A clear relationship between diabetes and cardiovascular disease has been established for decades. Despite this, the mechanisms by which diabetes contributes to plaque formation remain in question. Some of this confusion derives from studies in type 2 diabetics where multiple components of metabolic syndrome show proatherosclerotic effects independent of underlying diabetes. However, the hyperglycemia that defines the diabetic condition independently affects atherogenesis in cell culture systems, animal models, and human patients. Endothelial cell biology plays a central role in atherosclerotic plaque formation regulating vessel permeability, inflammation, and thrombosis. The current paper highlights the mechanisms by which hyperglycemia affects endothelial cell biology to promote plaque formation. 1. Cardiovascular Disease and Diabetes Mellitus Treatment of cardiovascular disease (CVD), manifesting in the form of myocardial infarction, stroke, and peripheral artery disease, represents one of biomedical sciences best success stories over the past several decades [1, 2]. Through clinical trials, epidemiology, and basic science, we have identified a host of risk factors and designed drugs targeting these risk factors that improve patient survival. The cholesterol-lowering statin family of therapeutics reduces the 5-year risk of cardiovascular-associated mortality by ~25% in patients with a history of prior CVD [3]. However, statins have not shown similar protection in patients without a prior history of CVD [4, 5], and CVD remains the leading cause of death in developed countries [2, 6]. Furthermore, the current obesity epidemic threatens to worsen the incidence of CVD in the coming years, undoing the progress we have made to this point [7]. More than 80% of the CVD-associated death and disability is attributed to atherosclerosis, the excessive accumulation of lipids, cholesterol, inflammatory cells, and connective tissue in the vessel wall [8, 9]. While clinically silent for decades, atherosclerotic plaques can grow to occlude the vessel lumen reducing blood flow to target tissues [8, 9]. Although this form of vessel occlusion can result in significant discomfort (e.g., angina pectoris), clinical events most often result from thrombus formation due to plaque deterioration or rupture resulting in a rapid cessation in blood flow to target tissue. Theories concerning the pathogenesis of atherosclerosis have changed over the years, maturing concomitantly with our understanding of vascular biology. We now know that atherosclerosis is a chronic inflammatory
References
[1]
R. Klingenberg and G. K. Hansson, “Treating inflammation in atherosclerotic cardiovascular disease: emerging therapies,” European Heart Journal, vol. 30, no. 23, pp. 2838–2844, 2009.
[2]
V. L. Roger, A. S. Go, D. M. Lloyd-Jones et al., “Heart disease and stroke statistics-2011 update: a report from the American heart association,” Circulation, vol. 123, no. 4, pp. e18–e209, 2010.
[3]
R. Collins, J. Armitage, S. Parish, et al., “Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions,” The Lancet, vol. 363, no. 9411, pp. 757–767, 2004.
[4]
P. Thavendiranathan, A. Bagai, M. A. Brookhart, and N. K. Choudhry, “Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials,” Archives of Internal Medicine, vol. 166, no. 21, pp. 2307–2313, 2006.
[5]
K. K. Ray, S. R. K. Seshasai, S. Erqou et al., “Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants,” Archives of Internal Medicine, vol. 170, no. 12, pp. 1024–1031, 2010.
[6]
S. Yusuf, S. Reddy, S. ？unpuu, and S. Anand, “Global burden of cardiovascular diseases. Part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization,” Circulation, vol. 104, no. 22, pp. 2746–2753, 2001.
[7]
S. L. Gortmaker, B. A. Swinburn, D. Levy et al., “Changing the future of obesity: science, policy, and action,” The Lancet, vol. 378, no. 9793, pp. 838–847, 2011.
[8]
R. Ross, “Atherosclerosis—an inflammatory disease,” New England Journal of Medicine, vol. 340, no. 2, pp. 115–126, 1999.
[9]
P. Libby, P. M. Ridker, and G. K. Hansson, “Progress and challenges in translating the biology of atherosclerosis,” Nature, vol. 473, no. 7347, pp. 317–325, 2011.
[10]
P. Libby, P. M. Ridker, and G. K. Hansson, “Inflammation in atherosclerosis. From pathophysiology to practice,” Journal of the American College of Cardiology, vol. 54, no. 23, pp. 2129–2138, 2009.
[11]
A. Daugherty, H. Lu, D. A. Howatt, and D. L. Rateri, “Modes of defining atherosclerosis in mouse models: relative merits and evolving standards,” Methods in Molecular Biology, vol. 573, pp. 1–15, 2009.
[12]
M. A. Gimbrone Jr, J. N. Topper, T. Nagel, K. R. Anderson, and G. Garcia-Carde？a, “Endothelial dysfunction, hemodynamic forces, and atherogenesis,” Annals of the New York Academy of Sciences, vol. 902, pp. 230–240, 2000.
[13]
C. Hahn and M. A. Schwartz, “Mechanotransduction in vascular physiology and atherogenesis,” Nature Reviews Molecular Cell Biology, vol. 10, no. 1, pp. 53–62, 2009.
[14]
K. Kornerup, B. G. Nordestgaard, T. K. Jensen et al., “Transendothelial exchange of low-density lipoprotein is unaffected by the presence of severe atherosclerosis,” Cardiovascular Research, vol. 64, no. 2, pp. 337–345, 2004.
[15]
L. R. Tannock and V. L. King, “Proteoglycan mediated lipoprotein retention: a mechanism of diabetic atherosclerosis,” Reviews in Endocrine and Metabolic Disorders, vol. 9, no. 4, pp. 289–300, 2008.
[16]
C. Mazière and J. C. Mazière, “Activation of transcription factors and gene expression by oxidized low-density lipoprotein,” Free Radical Biology and Medicine, vol. 46, no. 2, pp. 127–137, 2009.
[17]
E. Falk and A. Fernandez-Ortiz, “Role of thrombosis in atherosclerosis and its complications,” American Journal of Cardiology, vol. 75, no. 6, pp. 3B–11B, 1995.
[18]
P. Libby, “The molecular mechanisms of the thrombotic complications of atherosclerosis,” Journal of Internal Medicine, vol. 263, no. 5, pp. 517–527, 2008.
[19]
P. Libby, “Molecular and cellular mechanisms of the thrombotic complications of atherosclerosis,” Journal of lipid research, vol. 263, supplement 5, pp. S352–S357, 2009.
[20]
F. Henschen, “On the term diabetes in the works of Aretaeus and Galen,” Medical History, vol. 13, no. 2, pp. 190–192, 1969.
[21]
S. Wild, G. Roglic, A. Green, R. Sicree, and H. King, “Global prevalence of diabetes: estimates for the year 2000 and projections for 2030,” Diabetes Care, vol. 27, no. 5, pp. 1047–1053, 2004.
[22]
R. R. Little and D. B. Sacks, “HbA1c: how do we measure it and what does it mean?” Current Opinion in Endocrinology, Diabetes and Obesity, vol. 16, no. 2, pp. 113–118, 2009.
[23]
H. Ding and C. R. Triggle, “Endothelial cell dysfunction and the vascular complications associated with type 2 diabetes: assessing the health of the endothelium,” Vascular Health and Risk Management, vol. 1, no. 1, pp. 55–71, 2005.
[24]
N. Winer and J. R. Sowers, “Epidemiology of diabetes,” Journal of Clinical Pharmacology, vol. 44, no. 4, pp. 397–405, 2004.
[25]
L. Whiteley, S. Padmanabhan, D. Hole, and C. Isles, “Should diabetes be considered a coronary heart disease risk equivalent? results from 25 years of follow-up in the Renfrew and Paisley survey,” Diabetes Care, vol. 28, no. 7, pp. 1588–1593, 2005.
[26]
P. Pajunen, M. R. Taskinen, M. S. Nieminen, and M. Syv？nne, “Angiographic severity and extent of coronary artery disease in patients with type 1 diabetes mellitus,” American Journal of Cardiology, vol. 86, no. 10, pp. 1080–1085, 2000.
[27]
P. R. Moreno, A. M. Murcia, I. F. Palacios et al., “Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus,” Circulation, vol. 102, no. 18, pp. 2180–2184, 2000.
[28]
A. P. Burke, F. D. Kolodgie, A. Zieske et al., “Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 7, pp. 1266–1271, 2004.
[29]
D. de Zeeuw and S. J. L. Bakker, “Does the metabolic syndrome add to the diagnosis and treatment of cardiovascular disease?” Nature Clinical Practice Cardiovascular Medicine, vol. 5, supplement 1, pp. S10–S14, 2008.
[30]
K. Marinou, D. Tousoulis, A. S. Antonopoulos, E. Stefanadi, and C. Stefanadis, “Obesity and cardiovascular disease: from pathophysiology to risk stratification,” International Journal of Cardiology, vol. 138, no. 1, pp. 3–8, 2010.
[31]
L. F. van Gaal, I. L. Mertens, and C. E. de Block, “Mechanisms linking obesity with cardiovascular disease,” Nature, vol. 444, no. 7121, pp. 875–880, 2006.
[32]
M. J. Jarvisalo, M. Raitakari, J. O. Toikka et al., “Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes,” Circulation, vol. 109, no. 14, pp. 1750–1755, 2004.
[33]
H. C. McGill Jr, C. A. McMahan, A. W. Zieske, G. T. Malcom, R. E. Tracy, and J. P. Strong, “Effects of nonlipid risk factors on atherosclerosis in youth with a favorable lipoprotein profile,” Circulation, vol. 103, no. 11, pp. 1546–1550, 2001.
[34]
M. J. J？rvisalo, A. Putto-Laurila, L. Jartti et al., “Carotid artery intima-media thickness in children with type 1 diabetes,” Diabetes, vol. 51, no. 2, pp. 493–498, 2002.
[35]
S. Lenzen, “The mechanisms of alloxan- and streptozotocin-induced diabetes,” Diabetologia, vol. 51, no. 2, pp. 216–226, 2008.
[36]
S. Oehen, P. S. Ohashi, P. Aichele, K. Burki, H. Hengartner, and R. M. Zinkernagel, “Vaccination or tolerance to prevent diabetes,” European Journal of Immunology, vol. 22, no. 12, pp. 3149–3153, 1992.
[37]
J. Wang, T. Takeuchi, S. Tanaka et al., “A mutation in the insulin 2 gene induces diabetes with severe pancreatic β-cell dysfunction in the Mody mouse,” Journal of Clinical Investigation, vol. 103, no. 1, pp. 27–37, 1999.
[38]
J. Y. Jun, Z. Ma, and L. Segar, “Spontaneously diabetic Ins2(+/Akita): apoe-deficient mice exhibit exaggerated hypercholesterolemia and atherosclerosis,” American Journal of Physiology—Endocrinology and Metabolism, vol. 301, no. 1, pp. E145–E154, 2011.
[39]
C. Zhou, B. Pridgen, N. King, J. Xu, and J. L. Breslow, “Hyperglycemic Ins2AkitaLdlr-/- mice show severely elevated lipid levels and increased atherosclerosis: a model of type 1 diabetic macrovascular disease,” Journal of Lipid Research, vol. 52, no. 8, pp. 1483–1493, 2011.
[40]
H. Ding, M. Hashem, W. B. Wiehler et al., “Endothelial dysfunction in the streptozotocin-induced diabetic apoE-deficient mouse,” British Journal of Pharmacology, vol. 146, no. 8, pp. 1110–1118, 2005.
[41]
C. B. Renard, F. Kramer, F. Johansson et al., “Diabetes and diabetes-associated lipid abnormalities have distinct effects on initiation and progression of atherosclerotic lesions,” Journal of Clinical Investigation, vol. 114, no. 5, pp. 659–668, 2004.
[42]
M. I. J. Uusitupa, L. K. Niskanen, O. Siitonen, E. Voutilainen, and K. Pyorala, “Ten-year cardiovascular mortality in relation to risk factors and abnormalities in lipoprotein composition in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects,” Diabetologia, vol. 36, no. 11, pp. 1175–1184, 1993.
[43]
J. Kuusisto, L. Mykkanen, K. Pyorala, and M. Laakso, “Non-insulin-dependent diabetes and its metabolic control are important predictors of stroke in elderly subjects,” Stroke, vol. 25, no. 6, pp. 1157–1164, 1994.
[44]
The DCCT Group, “The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The diabetes control and complications trial research group,” The New England Journal of Medicine, vol. 329, no. 14, pp. 977–986, 1993.
[45]
D. M. Nathan, P. A. Cleary, J. Y. C. Backlund et al., “Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes,” New England Journal of Medicine, vol. 353, no. 25, pp. 2643–2653, 2005.
[46]
The UKPDS Group, “Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK prospective diabetes study (UKPDS) group,” The Lancet, vol. 352, no. 9131, pp. 837–853, 1998.
[47]
R. R. Holman, S. K. Paul, M. A. Bethel, D. R. Matthews, and H. A. W. Neil, “10-Year follow-up of intensive glucose control in type 2 diabetes,” New England Journal of Medicine, vol. 359, no. 15, pp. 1577–1589, 2008.
[48]
H. C. Gerstein, W. T. Friedewald, J. B. Buse et al., “Effects of intensive glucose lowering in type 2 diabetes,” New England Journal of Medicine, vol. 358, no. 24, pp. 2545–2559, 2008.
[49]
A. Patel, S. MacMahon, J. Chalmers et al., “Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes,” New England Journal of Medicine, vol. 358, no. 24, pp. 2560–2572, 2008.
[50]
W. Duckworth, C. Abraira, T. Moritz et al., “Glucose control and vascular complications in veterans with type 2 diabetes,” New England Journal of Medicine, vol. 360, no. 2, pp. 129–139, 2009.
[51]
H. F. Galley and N. R. Webster, “Physiology of the endothelium,” British Journal of Anaesthesia, vol. 93, no. 1, pp. 105–113, 2004.
[52]
J. S. Pober and W. C. Sessa, “Evolving functions of endothelial cells in inflammation,” Nature Reviews Immunology, vol. 7, no. 10, pp. 803–815, 2007.
[53]
A. W. Orr, J. M. Sanders, M. Bevard, E. Coleman, I. J. Sarembock, and M. A. Schwartz, “The subendothelial extracellular matrix modulates NF-κB activation by flow: a potential role in atherosclerosis,” Journal of Cell Biology, vol. 169, no. 1, pp. 191–202, 2005.
[54]
A. W. Orr, R. Stockton, M. B. Simmers et al., “Matrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis,” Journal of Cell Biology, vol. 176, no. 5, pp. 719–727, 2007.
[55]
K. Ley, C. Laudanna, M. I. Cybulsky, and S. Nourshargh, “Getting to the site of inflammation: the leukocyte adhesion cascade updated,” Nature Reviews Immunology, vol. 7, no. 9, pp. 678–689, 2007.
[56]
M. C. Bourdillon, R. N. Poston, C. Covacho, E. Chignier, G. Bricca, and J. L. McGregor, “ICAM-1 deficiency reduces atherosclerotic lesions in double-knockout mice (ApoE(-/-)/ICAM-1(-/-)) fed a fat or a chow diet,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 20, no. 12, pp. 2630–2635, 2000.
[57]
M. I. Cybulsky, K. Iiyama, H. Li et al., “A major role for VCAM-1, but not ICAM-1, in early atherosclerosis,” Journal of Clinical Investigation, vol. 107, no. 10, pp. 1255–1262, 2001.
[58]
K. Ley and Y. Huo, “VCAM-1 is critical in atherosclerosis,” Journal of Clinical Investigation, vol. 107, no. 10, pp. 1209–1210, 2001.
[59]
G. C. Gurtner, V. Davis, H. Li, M. J. McCoy, A. Sharpe, and M. I. Cybulsky, “Targeted disruption of the murine VCAM1 gene: essential role of VCAM-1 in chorioallantoic fusion and placentation,” Genes and Development, vol. 9, no. 1, pp. 1–14, 1995.
[60]
L. Gu, Y. Okada, S. K. Clinton et al., “Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice,” Molecular Cell, vol. 2, no. 2, pp. 275–281, 1998.
[61]
J. S. Pober and W. Min, “Endothelial cell dysfunction, injury and death,” Handbook of Experimental Pharmacology, no. 176, part 2, pp. 135–156, 2006.
[62]
G. M. Buga, M. E. Gold, J. M. Fukuto, and L. J. Ignarro, “Shear stress-induced release of nitric oxide from endothelial cells grown on beads,” Hypertension, vol. 17, no. 2, pp. 187–193, 1991.
[63]
J. L. Amezcua, G. J. Dusting, R. M. J. Palmer, and S. Moncada, “Acetylcholine induces vasodilatation in the rabbit isolated heart through the release of nitric oxide, the endogenous nitrovasodilator,” British Journal of Pharmacology, vol. 95, no. 3, pp. 830–834, 1988.
[64]
V. Lahera, M. G. Salom, M. J. Fiksen-Olsen, and J. C. Romero, “Mediatory role of endothelium-derived nitric oxide in renal vasodilatory and excretory effects of bradykinin,” American Journal of Hypertension, vol. 4, no. 3, part 1, pp. 260–262, 1991.
[65]
U. Scherrer, D. Randin, P. Vollenweider, L. Vollenweider, and P. Nicod, “Nitric oxide release accounts for insulin's vascular effects in humans,” Journal of Clinical Investigation, vol. 94, no. 6, pp. 2511–2515, 1994.
[66]
H. O. Steinberg, G. Brechtel, A. Johnson, N. Fineberg, and A. D. Baron, “Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release,” Journal of Clinical Investigation, vol. 94, no. 3, pp. 1172–1179, 1994.
[67]
H. Chen, M. Montagnani, T. Funahashi, I. Shimomura, and M. J. Quon, “Adiponectin stimulates production of nitric oxide in vascular endothelial cells,” Journal of Biological Chemistry, vol. 278, no. 45, pp. 45021–45026, 2003.
[68]
Y. Xia, A. L. Tsai, V. Berka, and J. L. Zweier, “Superoxide generation from endothelial nitric-oxide synthase: a Ca2+/calmodulin-dependent and tetrahydrobiopterin regulatory process,” Journal of Biological Chemistry, vol. 273, no. 40, pp. 25804–25808, 1998.
[69]
C. Antoniades, C. Shirodaria, P. Leeson et al., “Association of plasma asymmetrical dimethylarginine (ADMA) with elevated vascular superoxide production and endothelial nitric oxide synthase uncoupling: implications for endothelial function in human atherosclerosis,” European Heart Journal, vol. 30, no. 9, pp. 1142–1150, 2009.
[70]
C. Dumitrescu, R. Biondi, Y. Xia et al., “Myocardial ischemia results in tetrahydrobiopterin (BH4) oxidation with impaired endothelial function ameliorated by BHIN4,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 38, pp. 15081–15086, 2007.
[71]
C. A. Chen, T. Y. Wang, S. Varadharaj et al., “S-glutathionylation uncouples eNOS and regulates its cellular and vascular function,” Nature, vol. 468, no. 7327, pp. 1115–1120, 2010.
[72]
F. Giacco and M. Brownlee, “Oxidative stress and diabetic complications,” Circulation Research, vol. 107, no. 9, pp. 1058–1070, 2010.
[73]
Z. Fatehi-Hassanabad, C. B. Chan, and B. L. Furman, “Reactive oxygen species and endothelial function in diabetes,” European Journal of Pharmacology, vol. 636, no. 1–3, pp. 8–17, 2010.
[74]
N. G. Oberprieler, W. Roberts, A. M. Graham, S. Homer-Vanniasinkam, and K. M. Naseem, “cGMP-independent inhibition of integrin αIIbβ3-mediated platelet adhesion and outside-in signalling by nitric oxide,” FEBS Letters, vol. 581, no. 7, pp. 1529–1534, 2007.
[75]
W. Roberts, R. Riba, S. Homer-Vanniasinkam, R. W. Farndale, and K. M. Naseem, “Nitric oxide specifically inhibits integrin-mediated platelet adhesion and spreading on collagen,” Journal of Thrombosis and Haemostasis, vol. 6, no. 12, pp. 2175–2185, 2008.
[76]
A. Chigaev, Y. Smagley, and L. A. Sklar, “Nitric oxide/cGMP pathway signaling actively down-regulates α4β1-integrin affinity: an unexpected mechanism for inducing cell de-adhesion,” BMC Immunology, vol. 12, p. 28, 2011.
[77]
R. Draijer, D. E. Atsma, A. van der Laarse, and V. W. M. van Hinsbergh, “cGMP and nitric oxide modulate thrombin-induced endothelial permeability: regulation via different pathways in human aortic and umbilical vein endothelial cells,” Circulation Research, vol. 76, no. 2, pp. 199–208, 1995.
[78]
K. Matsushita, C. N. Morrell, B. Cambien et al., “Nitric oxide regulates exocytosis by S-nitrosylation of N-ethylmaleimide-sensitive factor,” Cell, vol. 115, no. 2, pp. 139–150, 2003.
[79]
R. de Caterina, P. Libby, H. B. Peng et al., “Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines,” Journal of Clinical Investigation, vol. 96, no. 1, pp. 60–68, 1995.
[80]
B. V. Khan, D. G. Harrison, M. T. Olbrych, R. W. Alexander, and R. M. Medford, “Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 17, pp. 9114–9119, 1996.
[81]
S. C. Tai, G. B. Robb, and P. A. Marsden, “Endothelial nitric oxide synthase: a new paradigm for gene regulation in the injured blood vessel,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 3, pp. 405–412, 2004.
[82]
D. J. Lefer, S. P. Jones, W. G. Girod et al., “Leukocyte-endothelial cell interactions in nitric oxide synthase- deficient mice,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 276, no. 6, part 2, pp. H1943–H1950, 1999.
[83]
R. D. Rudic, E. G. Shesely, N. Maeda, O. Smithies, S. S. Segal, and W. C. Sessa, “Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling,” Journal of Clinical Investigation, vol. 101, no. 4, pp. 731–736, 1998.
[84]
M. Ozaki, S. Kawashima, T. Yamashita et al., “Overexpression of endothelial nitric oxide synthase accelerates atherosclerotic lesion formation in apoE-deficient mice,” Journal of Clinical Investigation, vol. 110, no. 3, pp. 331–340, 2002.
[85]
T. S. Schmidt, E. McNeill, G. Douglas et al., “Tetrahydrobiopterin supplementation reduces atherosclerosis and vascular inflammation in apolipoprotein E-knockout mice,” Clinical Science, vol. 119, no. 3, pp. 131–142, 2010.
[86]
L. Li, W. Chen, A. Rezvan, H. Jo, and D. G. Harrison, “Tetrahydrobiopterin deficiency and nitric oxide synthase uncoupling contribute to atherosclerosis induced by disturbed flow,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 31, no. 7, pp. 1547–1554, 2011.
[87]
Y. Ding, N. D. Vaziri, R. Coulson, V. S. Kamanna, and D. D. Roh, “Effects of simulated hyperglycemia, insulin, and glucagon on endothelial nitric oxide synthase expression,” American Journal of Physiology—Endocrinology and Metabolism, vol. 279, no. 1, pp. E11–E17, 2000.
[88]
X. L. Du, D. Edelstein, S. Dimmeler, Q. Ju, C. Sui, and M. Brownlee, “Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site,” Journal of Clinical Investigation, vol. 108, no. 9, pp. 1341–1348, 2001.
[89]
M. Hamuro, J. Polan, M. Natarajan, and S. Mohan, “High glucose induced nuclear factor κ B mediated inhibition of endothelial cell migration,” Atherosclerosis, vol. 162, no. 2, pp. 277–287, 2002.
[90]
P. Luppi, V. Cifarelli, H. Tse, J. Piganelli, and M. Trucco, “Human C-peptide antagonises high glucose-induced endothelial dysfunction through the nuclear factor-κB pathway,” Diabetologia, vol. 51, no. 8, pp. 1534–1543, 2008.
[91]
R. Piga, Y. Naito, S. Kokura, O. Handa, and T. Yoshikawa, “Short-term high glucose exposure induces monocyte-endothelial cells adhesion and transmigration by increasing VCAM-1 and MCP-1 expression in human aortic endothelial cells,” Atherosclerosis, vol. 193, no. 2, pp. 328–334, 2007.
[92]
M. Morigi, S. Angioletti, B. Imberti et al., “Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-kB-dependent fashion,” Journal of Clinical Investigation, vol. 101, no. 9, pp. 1905–1915, 1998.
[93]
I. Manduteanu, M. Voinea, G. Serban, and M. Simionescu, “High glucose induces enhanced monocyte adhesion to valvular endothelial cells via a mechanism involving ICAM-1, VCAM-1 and CD18,” Endothelium, vol. 6, no. 4, pp. 315–324, 1999.
[94]
C. Esposito, G. Fasoli, A. Plati et al., “Long-term exposure to high glucose up-regulates VCAM-induced endothelial cell adhesiveness to PBMC,” Kidney International, vol. 59, no. 5, pp. 1842–1849, 2001.
[95]
L. Piconi, L. Quagliaro, R. da Ros et al., “Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: the role of poly(ADP-ribose) polymerase,” Journal of Thrombosis and Haemostasis, vol. 2, no. 8, pp. 1453–1459, 2004.
[96]
J. A. Kim, J. A. Berliner, R. D. Natarajan, and J. L. Nadler, “Evidence that glucose increases monocyte binding to human aortic endothelial cells,” Diabetes, vol. 43, no. 9, pp. 1103–1107, 1994.
[97]
A. El-Osta, D. Brasacchio, D. Yao et al., “Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia,” Journal of Experimental Medicine, vol. 205, no. 10, pp. 2409–2417, 2008.
[98]
R. P. Patel, D. Moellering, J. Murphy-Ullrich, H. Jo, J. S. Beckman, and V. M. Darley-Usmar, “Cell signaling by reactive nitrogen and oxygen species in atherosclerosis,” Free Radical Biology and Medicine, vol. 28, no. 12, pp. 1780–1794, 2000.
[99]
G. P. Sorescu, H. Song, S. L. Tressel et al., “Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress induces monocyte adhesion by stimulating reactive oxygen species production from a Nox1-based NADPH oxidase,” Circulation Research, vol. 95, no. 8, pp. 773–779, 2004.
[100]
A. W. Orr, C. Hahn, B. R. Blackman, and M. A. Schwartz, “P21-activated kinase signaling regulates oxidant-dependent NF-κB activation by flow,” Circulation Research, vol. 103, no. 6, pp. 671–679, 2008.
[101]
D. Han, M. D. Ybanez, S. Ahmadi, K. Yeh, and N. Kaplowitz, “Redox regulation of tumor necrosis factor signaling,” Antioxidants and Redox Signaling, vol. 11, no. 9, pp. 2245–2263, 2009.
[102]
Q. Li and J. F. Engelhardt, “Interleukin-1β induction of NFκB is partially regulated by H2O2-mediated activation of NFκB-inducing kinase,” Journal of Biological Chemistry, vol. 281, no. 3, pp. 1495–1505, 2006.
[103]
J. Liu, F. Yang, X. -P. Yang, M. Jankowski, and P. J. Pagano, “NAD(P)H oxidase mediates angiotensin II-induced vascular macrophage infiltration and medial hypertrophy,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 5, pp. 776–782, 2003.
[104]
L. Cominacini, A. F. Pasini, U. Garbin et al., “Oxidized low density lipoprotein (ox-LDL) binding to ox-LDL receptor-1 in endothelial cells induces the activation of NF-κB through an increased production of intracellular reactive oxygen species,” Journal of Biological Chemistry, vol. 275, no. 17, pp. 12633–12638, 2000.
[105]
R. P. Brandes and K. Schroder, “Differential vascular functions of Nox family NADPH oxidases,” Current Opinion in Lipidology, vol. 19, no. 5, pp. 513–518, 2008.
[106]
G. Gloire, S. Legrand-Poels, and J. Piette, “NF-κB activation by reactive oxygen species: fifteen years later,” Biochemical Pharmacology, vol. 72, no. 11, pp. 1493–1505, 2006.
[107]
C. G. Kevil, T. Oshima, B. Alexander, L. L. Coe, and J. S. Alexander, “H2O2-mediated permeability: role of MAPK and occludin,” American Journal of Physiology—Cell Physiology, vol. 279, no. 1, pp. C21–C30, 2000.
[108]
N. Okayama, C. G. Kevil, L. Correia et al., “Nitric oxide enhances hydrogen peroxide-mediated endothelial permeability in vitro,” American Journal of Physiology—Cell Physiology, vol. 273, no. 5, part 1, pp. C1581–C1587, 1997.
[109]
J. Galle, T. Hansen-Hagge, C. Wanner, and S. Seibold, “Impact of oxidized low density lipoprotein on vascular cells,” Atherosclerosis, vol. 185, no. 2, pp. 219–226, 2006.
[110]
U. Landmesser, S. Dikalov, S. R. Price et al., “Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension,” Journal of Clinical Investigation, vol. 111, no. 8, pp. 1201–1209, 2003.
[111]
S. P. Wolff, Z. Y. Jiang, and J. V. Hunt, “Protein glycation and oxidative stress in diabetes mellitus and ageing,” Free Radical Biology and Medicine, vol. 10, no. 5, pp. 339–352, 1991.
[112]
U. J. Eriksson and L. A. H. Borg, “Diabetes and embryonic malformations: role of substrate-induced free- oxygen radical production for dysmorphogenesis in cultured rat embryos,” Diabetes, vol. 42, no. 3, pp. 411–419, 1993.
[113]
S. Cai, J. Khoo, and K. M. Channon, “Augmented BH4 by gene transfer restores nitric oxide synthase function in hyperglycemic human endothelial cells,” Cardiovascular Research, vol. 65, no. 4, pp. 823–831, 2005.
[114]
Z. Y. Jiang, A. C. S. Woollard, and S. P. Wolff, “Hydrogen peroxide production during experimental protein glycation,” FEBS Letters, vol. 268, no. 1, pp. 69–71, 1990.
[115]
D. P. Gelain, R. J. S. Dalmolin, V. L. Belau, J. C. F. Moreira, F. Klamt, and M. A. A. Castro, “A systematic review of human antioxidant genes,” Frontiers in Bioscience, vol. 14, no. 12, pp. 4457–4463, 2009.
[116]
L. J. Mandarino, J. Finlayson, and J. R. Hassell, “High glucose downregulates glucose transport activity in retinal capillary pericytes but not endothelial cells,” Investigative Ophthalmology and Visual Science, vol. 35, no. 3, pp. 964–972, 1994.
[117]
M. H. Zou, C. Shi, and R. A. Cohen, “Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite,” Journal of Clinical Investigation, vol. 109, no. 6, pp. 817–826, 2002.
[118]
G. Basta, G. Lazzerini, S. del Turco, G. M. Ratto, A. M. Schmidt, and R. de Caterina, “At least 2 distinct pathways generating reactive oxygen species mediate vascular cell adhesion molecule-1 induction by advanced glycation end products,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 7, pp. 1401–1407, 2005.
[119]
T. Nishikawa, D. Edelstein, X. L. Du et al., “Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage,” Nature, vol. 404, no. 6779, pp. 787–790, 2000.
[120]
R. Recchioni, F. Marcheselli, F. Moroni, and C. Pieri, “Apoptosis in human aortic endothelial cells induced by hyperglycemic condition involves mitochondrial depolarization and is prevented by N-acetyl-L-cysteine,” Metabolism, vol. 51, no. 11, pp. 1384–1388, 2002.
[121]
H. Tsuneki, N. Sekizaki, T. Suzuki et al., “Coenzyme Q10 prevents high glucose-induced oxidative stress in human umbilical vein endothelial cells,” European Journal of Pharmacology, vol. 566, no. 1–3, pp. 1–10, 2007.
[122]
L. Quagliaro, L. Piconi, R. Assaloni et al., “Intermittent high glucose enhances ICAM-1, VCAM-1 and E-selectin expression in human umbilical vein endothelial cells in culture: the distinct role of protein kinase C and mitochondrial superoxide production,” Atherosclerosis, vol. 183, no. 2, pp. 259–267, 2005.
[123]
L. Quagliaro, L. Piconi, R. Assaloni, R. da Ros, C. Szabó, and A. Ceriello, “Primary role of superoxide anion generation in the cascade of events leading to endothelial dysfunction and damage in high glucose treated HUVEC,” Nutrition, Metabolism and Cardiovascular Diseases, vol. 17, no. 4, pp. 257–267, 2007.
[124]
P. S. Tsao, J. Niebauer, R. Buitrago et al., “Interaction of diabetes and hypertension on determinants of endothelial adhesiveness,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 18, no. 6, pp. 947–953, 1998.
[125]
X.-Q. Yang, Y.-Y. Wang, and A. F. Chen, “Increased superoxide contributes to enhancement of vascular contraction in INS2AKITA diabetic mice, an autosomal dominant mutant model,” Clinical and Experimental Pharmacology and Physiology, vol. 35, no. 9, pp. 1097–1103, 2008.
[126]
A. Cumaoglu, G. Ozansoy, A. M. Irat, A. Aricioglu, C. Karasu, and N. Ari, “Effect of long term, non cholesterol lowering dose of fluvastatin treatment on oxidative stress in brain and peripheral tissues of streptozotocin-diabetic rats,” European Journal of Pharmacology, vol. 654, no. 1, pp. 80–85, 2011.
[127]
B. Tesfamariam and R. A. Cohen, “Free radicals mediate endothelial cell dysfunction caused by elevated glucose,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 263, no. 2, part 2, pp. H321–H326, 1992.
[128]
G. M. Pieper, “Divergent actions of chronic insulin treatment in vivo versus acute treatment ex vivo on diabetic-induced endothelial dysfunction,” Life Sciences, vol. 60, no. 25, pp. PL371–PL376, 1997.
[129]
G. M. Pieper and W. Siebeneich, “Oral administration of the antioxidant, N-acetylcysteine, abrogates diabetes-induced endothelial dysfunction,” Journal of Cardiovascular Pharmacology, vol. 32, no. 1, pp. 101–105, 1998.
[130]
P. Lewis, N. Stefanovic, J. Pete et al., “Lack of the antioxidant enzyme glutathione peroxidase-1 accelerates atherosclerosis in diabetic apolipoprotein E-deficient mice,” Circulation, vol. 115, no. 16, pp. 2178–2187, 2007.
[131]
S. V. Brodsky, O. Gealekman, J. Chen et al., “Prevention and reversal of premature endothelial cell senescence and vasculopathy in obesity-induced diabetes by ebselen,” Circulation Research, vol. 94, no. 3, pp. 377–384, 2004.
[132]
P. Chew, D. Y. C. Yuen, P. Koh et al., “Site-specific antiatherogenic effect of the antioxidant ebselen in the diabetic apolipoprotein E-deficient mouse,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 29, no. 6, pp. 823–830, 2009.
[133]
C. L. Allen and U. Bayraktutan, “Antioxidants attenuate hyperglycaemia-mediated brain endothelial cell dysfunction and blood-brain barrier hyperpermeability,” Diabetes, Obesity and Metabolism, vol. 11, no. 5, pp. 480–490, 2009.
[134]
L. Dang, J. P. Seale, and X. Qu, “High glucose-induced human umbilical vein endothelial cell hyperpermeability is dependent on protein kinase C activation and independent of the Ca2+-nitric oxide signalling pathway,” Clinical and Experimental Pharmacology and Physiology, vol. 32, no. 9, pp. 771–776, 2005.
[135]
G. R. Drummond, S. Selemidis, K. K. Griendling, and C. G. Sobey, “Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets,” Nature Reviews Drug Discovery, vol. 10, no. 6, pp. 453–471, 2011.
[136]
S. Yusuf, G. Dagenais, J. Pogue, J. Bosch, and P. Sleight, “Vitamin E supplementation and cardiovascular events in high-risk patients. The heart outcomes prevention evaluation study investigators,” The New England Journal of Medicine, vol. 342, no. 3, pp. 154–160, 2000.
[137]
M. Boaz, S. Smetana, T. Weinstein et al., “Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial,” The Lancet, vol. 356, no. 9237, pp. 1213–1218, 2000.
[138]
E. M. Lonn, S. Yusuf, V. Dzavik et al., “Effects of Ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with Ramipril and vitamin E (SECURE),” Circulation, vol. 103, no. 7, pp. 919–925, 2001.
[139]
M. Sacco, F. Pellegrini, M. C. Roncaglioni, F. Avanzini, G. Tognoni, and A. Nicolucci, “Primary prevention of cardiovascular events with low dose aspirin and vitamin E in type 2 diabetic patients: results of the primary prevention project (PPP) trial,” Diabetes Care, vol. 26, no. 12, pp. 3264–3272, 2003.
[140]
S. R. Steinhubl, “Why have antioxidants failed in clinical trials?” American Journal of Cardiology, vol. 101, no. 10, pp. 14D–19D, 2008.
[141]
E. S. Slavina, A. Madanat, A. Pankov, et al., “Diabetes mellitus and atherosclerosis,” New England Journal of Medicine, vol. 317, no. 13, p. 836, 1987.
[142]
R. Singh, A. Barden, T. Mori, and L. Beilin, “Advanced glycation end-products: a review,” Diabetologia, vol. 44, no. 2, pp. 129–146, 2001.
[143]
W. G. John, M. R. Gray, D. L. Bates, and J. L. Beacham, “Enzyme immunoassay—a new technique for estimating hemoglobin A1c,” Clinical Chemistry, vol. 39, no. 4, pp. 663–666, 1993.
[144]
T. P. Degenhardt, S. R. Thorpe, and J. W. Baynes, “Chemical modification of proteins by methylglyoxal,” Cellular and Molecular Biology (Noisy-le-Grand), vol. 44, no. 7, pp. 1139–1145, 1998.
[145]
M. Brownlee, “Biochemistry and molecular cell biology of diabetic complications,” Nature, vol. 414, no. 6865, pp. 813–820, 2001.
[146]
P. J. Thornalley, “The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life,” Biochemical Journal, vol. 269, no. 1, pp. 1–11, 1990.
[147]
K. J. Wells-Knecht, D. V. Zyzak, J. E. Litchfield, S. R. Thorpe, and J. W. Baynes, “Mechanism of autoxidative glycosylation: identification of glyoxal and arabinose as intermediates in the autoxidative modification of proteins by glucose,” Biochemistry, vol. 34, no. 11, pp. 3702–3709, 1995.
[148]
M. C. Wells-Knecht, S. R. Thorpe, and J. W. Baynes, “Pathways of formation of glycoxidation products during glycation of collagen,” Biochemistry, vol. 34, no. 46, pp. 15134–15141, 1995.
[149]
P. J. Thornalley, “Protecting the genome: defence against nucleotide glycation and emerging role of glyoxalase I overexpression in multidrug resistance in cancer chemotherapy,” Biochemical Society Transactions, vol. 31, no. 6, pp. 1372–1377, 2003.
[150]
M. Morcos, X. Du, F. Pfisterer et al., “Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in caenorhabditis elegans,” Aging Cell, vol. 7, no. 2, pp. 260–269, 2008.
[151]
M. Neeper, A. M. Schmidt, J. Brett et al., “Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins,” Journal of Biological Chemistry, vol. 267, no. 21, pp. 14998–15004, 1992.
[152]
C. Karasu, “Glycoxidative stress and cardiovascular complications in experimentally-induced diabetes: effects of antioxidant treatment,” The Open Cardiovascular Medicine Journal, vol. 4, pp. 240–256, 2010.
[153]
S. D. Yan, A. M. Schmidt, G. M. Anderson et al., “Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins,” Journal of Biological Chemistry, vol. 269, no. 13, pp. 9889–9897, 1994.
[154]
J. L. Wautier and P. J. Guillausseau, “Advanced glycation end products, their receptors and diabetic angiopathy,” Diabetes and Metabolism, vol. 27, no. 5, part 1, pp. 535–542, 2001.
[155]
A. M. Schmidt, O. Hori, J. X. Chen et al., “Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and in mice: a potential mechanism for the accelerated vasculopathy of diabetes,” Journal of Clinical Investigation, vol. 96, no. 3, pp. 1395–1403, 1995.
[156]
K. Higai, A. Shimamura, and K. Matsumoto, “Amadori-modified glycated albumin predominantly induces E-selectin expression on human umbilical vein endothelial cells through NADPH oxidase activation,” Clinica Chimica Acta, vol. 367, no. 1-2, pp. 137–143, 2006.
[157]
B. Xu, Y. Ji, K. Yao, Y. X. Cao, and A. Ferro, “Inhibition of human endothelial cell nitric oxide synthesis by advanced glycation end-products but not glucose: relevance to diabetes,” Clinical Science, vol. 109, no. 5, pp. 439–446, 2005.
[158]
B. Xu, R. Chibber, D. Ruggerio, E. Kohner, J. Ritter, and A. Ferro, “Impairment of vascular endothelial nitric oxide synthase activity by advanced glycation end products,” FASEB journal, vol. 17, no. 10, pp. 1289–1291, 2003.
[159]
L. Gao, W.-H. Liu, N.-N. Luan, C. Feng, and T. Shang, “[Correlation between the expression of high mobility group box 1 and receptor for advanced glycation end products and the onset of pre-eclampsia],” Zhonghua Fu Chan Ke Za Zhi, vol. 43, no. 10, pp. 746–750, 2008.
[160]
W. Cai, J. C. He, L. Zhu, C. Lu, and H. Vlassara, “Advanced glycation end product (AGE) receptor 1 suppresses cell oxidant stress and activation signaling via EGF receptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 37, pp. 13801–13806, 2006.
[161]
Y. Ishibashi, T. Matsui, M. Takeuchi, and S. I. Yamagishi, “Vardenafil, an inhibitor of phosphodiesterase-5, blocks advanced glycation end product (AGE)-induced up-regulation of monocyte chemoattractant protein-1 mRNA levels in endothelial cells by suppressing AGE receptor (RAGE) expression via elevation of cGMP,” Clinical and Experimental Medicine, vol. 11, no. 2, pp. 131–135, 2011.
[162]
D. Yao and M. Brownlee, “Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands,” Diabetes, vol. 59, no. 1, pp. 249–255, 2010.
[163]
D. R. Sell and V. M. Monnir, “Structure elucidation of a senescence cross-link from human extracellular matrix. Implication of pentoses in the aging process,” Journal of Biological Chemistry, vol. 264, no. 36, pp. 21597–21602, 1989.
[164]
R. Bucala, K. J. Tracey, and A. Cerami, “Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes,” Journal of Clinical Investigation, vol. 87, no. 2, pp. 432–438, 1991.
[165]
M. Laga, A. Cottyn, F. van Herreweghe et al., “Methylglyoxal suppresses TNF-α-induced NF-κB activation by inhibiting NF-κB DNA-binding,” Biochemical Pharmacology, vol. 74, no. 4, pp. 579–589, 2007.
[166]
R. Bucala and H. Vlassara, “Advanced glycosylation end products in diabetic renal and vascular disease,” American Journal of Kidney Diseases, vol. 26, no. 6, pp. 875–888, 1995.
[167]
H. Tanaka, F. A. Dinenno, K. D. Monahan, C. M. Clevenger, C. A. DeSouza, and D. R. Seals, “Aging, habitual exercise, and dynamic arterial compliance,” Circulation, vol. 102, no. 11, pp. 1270–1275, 2000.
[168]
B. Corman, M. Duriez, P. Poitevin et al., “Aminoguanidine prevents age-related arterial stiffening and cardiac hypertrophy,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 3, pp. 1301–1306, 1998.
[169]
A. Goldin, J. A. Beckman, A. M. Schmidt, and M. A. Creager, “Advanced glycation end products: sparking the development of diabetic vascular injury,” Circulation, vol. 114, no. 6, pp. 597–605, 2006.
[170]
J. Diez, “Arterial stiffness and extracellular matrix,” Advances in Cardiology, vol. 44, pp. 76–95, 2007.
[171]
M. Hogan, A. Cerami, and R. Bucala, “Advanced glycosylation endproducts block the antiproliferative effect of nitric oxide. Role in the vascular and renal complications of diabetes mellitus,” Journal of Clinical Investigation, vol. 90, no. 3, pp. 1110–1115, 1992.
[172]
S. D. Funk, A. Yurdagul, J. M. Green, K. A. Jhaveri, M. A. Schwartz, and A. W. Orr, “Matrix-specific protein kinase a signaling regulates p21-activated kinase activation by flow in endothelial cells,” Circulation Research, vol. 106, no. 8, pp. 1394–1403, 2010.
[173]
C. S. Haitoglou, E. C. Tsilibary, M. Brownlee, and A. S. Charonis, “Altered cellular interactions between endothelial cells and nonenzymatically glucosylated laminin/type IV collagen,” Journal of Biological Chemistry, vol. 267, no. 18, pp. 12404–12407, 1992.
[174]
A. S. Charonis, L. A. Reger, J. E. Dege et al., “Laminin alterations after in vitro nonenzymatic glycosylation,” Diabetes, vol. 39, no. 7, pp. 807–814, 1990.
[175]
H. Yamawaki, K. Saito, M. Okada, and Y. Hara, “Methylglyoxal mediates vascular inflammation via JNK and p38 in human endothelial cells,” American Journal of Physiology—Cell Physiology, vol. 295, no. 6, pp. C1510–C1517, 2008.
[176]
G. Tang, Y. Minemoto, B. Dibling et al., “Inhibition of JNK activation through NF-κB target genes,” Nature, vol. 414, no. 6861, pp. 313–317, 2001.
[177]
W. H. Chan and H. J. Wu, “Methylglyoxal and high glucose co-treatment induces apoptosis or necrosis in human umbilical vein endothelial cells,” Journal of Cellular Biochemistry, vol. 103, no. 4, pp. 1144–1157, 2008.
[178]
N. Younis, R. Sharma, H. Soran, V. Charlton-Menys, M. Elseweidy, and P. N. Durrington, “Glycation as an atherogenic modification of LDL,” Current Opinion in Lipidology, vol. 19, no. 4, pp. 378–384, 2008.
[179]
L. Toma, C. S. Stancu, G. M. Botez, A. V. Sima, and M. Simionescu, “Irreversibly glycated LDL induce oxidative and inflammatory state in human endothelial cells; added effect of high glucose,” Biochemical and Biophysical Research Communications, vol. 390, no. 3, pp. 877–882, 2009.
[180]
G. M. Ma, A. J. Halayko, G. L. Stelmack et al., “Effects of oxidized and glycated low-density lipoproteins on transcription and secretion of plasminogen activator inhibitor-1 in vascular endothelial cells,” Cardiovascular Pathology, vol. 15, no. 1, pp. 3–10, 2006.
[181]
G. V. Sangle, S. K. R. Chowdhury, X. Xie, G. L. Stelmack, A. J. Halayko, and G. X. Shen, “Impairment of mitochondrial respiratory chain activity in aortic endothelial cells induced by glycated low-density lipoprotein,” Free Radical Biology and Medicine, vol. 48, no. 6, pp. 781–790, 2010.
[182]
Y. Dong, Y. Wu, M. Wu et al., “Activation of protease calpain by oxidized and glycated LDL increases the degradation of endothelial nitric oxide synthase,” Journal of Cellular and Molecular Medicine, vol. 13, no. 9, pp. 2899–2910, 2009.
[183]
A. M. Watson, A. Soro-Paavonen, K. Sheehy et al., “Delayed intervention with AGE inhibitors attenuates the progression of diabetes-accelerated atherosclerosis in diabetic apolipoprotein E knockout mice,” Diabetologia, vol. 54, no. 3, pp. 681–689, 2011.
[184]
J. M. Forbes, L. T. L. Yee, V. Thallas et al., “Advanced glycation end product-interventions reduce diabetes-accelerated atherosclerosis,” Diabetes, vol. 53, no. 7, pp. 1813–1823, 2004.
[185]
D. A. Kass, E. P. Shapiro, M. Kawaguchi et al., “Improved arterial compliance by a novel advanced glycation end-product crosslink breaker,” Circulation, vol. 104, no. 13, pp. 1464–1470, 2001.
[186]
M. A. Zieman, “A heart that keeps on beating,” Behavioral Healthcare, vol. 27, no. 9, pp. 22–26, 2007.
[187]
O. Brouwers, P. M. Niessen, I. Ferreira et al., “Overexpression of glyoxalase-I reduces hyperglycemiainduced levels of advanced glycation end products and oxidative stress in diabetic rats,” Journal of Biological Chemistry, vol. 286, no. 2, pp. 1374–1380, 2011.
[188]
L. Engelen, I. Ferreira, O. Brouwers et al., “Polymorphisms in glyoxalase 1 gene are not associated with vascular complications: the Hoorn and CoDAM studies,” Journal of Hypertension, vol. 27, no. 7, pp. 1399–1403, 2009.
[189]
J. C. Wu, X. H. Li, Y. D. Peng, J. B. Wang, J. F. Tang, and Y. F. Wang, “Association of two glyoxalase 1 gene polymorphisms with nephropathy and retinopathy in type 2 diabetes,” Journal of Endocrinological Investigation, vol. 34, no. 10, pp. e343–e348, 2011.
[190]
L. Park, K. G. Raman, K. J. Lee et al., “Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts,” Nature Medicine, vol. 4, no. 9, pp. 1025–1031, 1998.
[191]
L. G. Bucciarelli, T. Wendt, W. Qu et al., “RAGE blockade stabilizes established atherosclerosis in diabetic apolipoprotein E-null mice,” Circulation, vol. 106, no. 22, pp. 2827–2835, 2002.
[192]
E. Harja, D. X. Bu, B. I. Hudson et al., “Vascular and inflammatory stresses mediate atherosclerosis via RAGE and its ligands in apoE-/- mice,” Journal of Clinical Investigation, vol. 118, no. 1, pp. 183–194, 2008.
[193]
N. A. Calcutt, M. E. Cooper, T. S. Kern, and A. M. Schmidt, “Therapies for hyperglycaemia-induced diabetic complications: from animal models to clinical trials,” Nature Reviews Drug Discovery, vol. 8, no. 5, pp. 417–429, 2009.
[194]
R. G. Gonzalez, P. Barnett, and J. Aguayo, “Direct measurement of polyol pathway activity in the ocular lens,” Diabetes, vol. 33, no. 2, pp. 196–199, 1984.
[195]
A. D. Morrison, R. S. Clements Jr, S. B. Travis, F. Oski, and A. I. Winegrad, “Glucose utilization by the polyol pathway in human erythrocytes,” Biochemical and Biophysical Research Communications, vol. 40, no. 1, pp. 199–205, 1970.
[196]
S. K. Srivastava, K. V. Ramana, and A. Bhatnagar, “Role of aldose reductase and oxidative damage in diabetes and the consequent potential for therapeutic options,” Endocrine Reviews, vol. 26, no. 3, pp. 380–392, 2005.
[197]
R. Ramasamy and I. J. Goldberg, “Aldose reductase and cardiovascular diseases, creating human-like diabetic complications in an experimental model,” Circulation Research, vol. 106, no. 9, pp. 1449–1458, 2010.
[198]
J. H. Kinoshita, D. Dvornik, M. Kramil, and K. H. Gabbay, “The effect of an aldose reductase inhibitor on the galactose-exposed rabbit lens,” Biochimica et Biophysica Acta, vol. 158, no. 3, pp. 472–475, 1968.
[199]
S. D. Varma and J. H. Kinoshita, “Inhibition of lens aldose reductase by flavonoids: their possible role in the prevention of diabetic cataracts,” Biochemical Pharmacology, vol. 25, no. 22, pp. 2505–2513, 1976.
[200]
S. D. Varma, A. Mizuno, and J. H. Kinoshita, “Diabetic cataracts and flavonoids,” Science, vol. 195, no. 4274, pp. 205–206, 1977.
[201]
S. K. Srivastava and N. H. Ansari, “Prevention of sugar-induced cataractogenesis in rats by butylated hydroxytoluene,” Diabetes, vol. 37, no. 11, pp. 1505–1508, 1988.
[202]
N. H. Ansari and S. K. Srivastava, “Allopurinol promotes and butylated hydroxy toluene prevents sugar-induced cataractogenesis,” Biochemical and Biophysical Research Communications, vol. 168, no. 3, pp. 939–943, 1990.
[203]
N. H. Ansari, A. Bhatnagar, E. Fulep, P. Khanna, and S. K. Srivastava, “Trolox protects hyperglycemia-induced cataractogenesis in cultured rat lens,” Research Communications in Chemical Pathology and Pharmacology, vol. 84, no. 1, pp. 93–104, 1994.
[204]
T. S. Kern and R. L. Engerman, “Immunohistochemical distribution of aldose reductase,” Histochemical Journal, vol. 14, no. 3, pp. 507–515, 1982.
[205]
H. Omi, N. Okayama, M. Shimizu et al., “Participation of high glucose concentrations in neutrophil adhesion and surface expression of adhesion molecules on cultured human endothelial cells: effect of antidiabetic medicines,” Journal of Diabetes and its Complications, vol. 16, no. 3, pp. 201–208, 2002.
[206]
K. V. Ramana, A. Bhatnagar, and S. K. Srivastava, “Inhibition of aldose reductase attenuates TNF-α-induced expression of adhesion molecules in endothelial cells,” FASEB Journal, vol. 18, no. 11, pp. 1209–1218, 2004.
[207]
S. Srivastava, M. Spite, J. O. Trent, M. B. West, Y. Ahmed, and A. Bhatnagar, “Aldose reductase-catalyzed reduction of aldehyde phospholipids,” Journal of Biological Chemistry, vol. 279, no. 51, pp. 53395–53406, 2004.
[208]
K. V. Ramana, B. L. Dixit, S. Srivastava, G. K. Balendiran, S. K. Srivastava, and A. Bhatnagar, “Selective recognition of glutathiolated aldehydes by aldose reductase,” Biochemistry, vol. 39, no. 40, pp. 12172–12180, 2000.
[209]
K. V. Ramana and S. K. Srivastava, “Aldose reductase: a novel therapeutic target for inflammatory pathologies,” International Journal of Biochemistry and Cell Biology, vol. 42, no. 1, pp. 17–20, 2010.
[210]
S. Srivastava, E. Vladykovskaya, O. A. Barski et al., “Aldose reductase protects against early atherosclerotic lesion formation in apolipoprotein E-null mice,” Circulation Research, vol. 105, no. 8, pp. 793–802, 2009.
[211]
S. Vedantham, H. Noh, and R. Ananthakrishnan, “Human aldose reductase expression accelerates atherosclerosis in diabetic apolipoprotein E-/- mice,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 31, no. 8, pp. 1805–1813, 2011.
[212]
R. K. Vikramadithyan, Y. Hu, H. L. Noh et al., “Human aldose reductase expression accelerates diabetic atherosclerosis in transgenic mice,” Journal of Clinical Investigation, vol. 115, no. 9, pp. 2434–2443, 2005.
[213]
A. G. Rajapakse, X. F. Ming, J. M. Carvas, and Z. Yang, “The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 296, no. 3, pp. H815–H822, 2009.
[214]
H. Goldberg, C. Whiteside, and I. G. Fantus, “O-linked β-N-acetylglucosa mine supports p38 MAPK activation by high glucose in glomerular mesangial cells,” American Journal of Physiology'Endocrinology and Metabolism, vol. 301, no. 4, pp. E713–E726, 2011.
[215]
R. S. Haltiwanger, M. A. Blomberg, and G. W. Hart, “Glycosylation of nuclear and cytoplasmic proteins. Purification and characterization of a uridine diphospho-N-acetylglucosamine: polypeptide β-N- acetylglucosaminyltransferase,” Journal of Biological Chemistry, vol. 267, no. 13, pp. 9005–9013, 1992.
[216]
R. S. Haltiwanger, G. D. Holt, and G. W. Hart, “Enzymatic addition of O-GlcNAc to nuclear and cytoplasmic proteins. Identification of a uridine diphospho-N-acetylglucosamine: peptide β-N-acetylglucosaminyltransferase,” Journal of Biological Chemistry, vol. 265, no. 5, pp. 2563–2568, 1990.
[217]
B. Laczy, B. G. Hill, K. Wang et al., “Protein O-GlcNAcylation: a new signaling paradigm for the cardiovascular system,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 296, no. 1, pp. H13–H28, 2009.
[218]
B. Laczy, S. A. Marsh, C. A. Brocks, I. Wittmann, and J. C. Chatham, “Inhibition of O-GlcNAcase in perfused rat hearts by NAG-thiazolines at the time of reperfusion is cardioprotective in an O-GlcNAc-dependent manner,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 299, no. 5, pp. H1715–H1727, 2010.
[219]
T. Wu, H. Zhou, Z. Jin et al., “Cardioprotection of salidroside from ischemia/reperfusion injury by increasing N-acetylglucosamine linkage to cellular proteins,” European Journal of Pharmacology, vol. 613, no. 1–3, pp. 93–99, 2009.
[220]
Y. Ju, J. Hua, K. Sakamoto, H. Ogawa, and I. Nagaoka, “Modulation of TNF-α-induced endothelial cell activation by glucosamine, a naturally occurring amino monosaccharide,” International Journal of Molecular Medicine, vol. 22, no. 6, pp. 809–815, 2008.
[221]
Y. Ju, J. Hua, K. Sakamoto, H. Ogawa, and I. Nagaoka, “Glucosamine, a naturally occurring amino monosaccharide modulates LL-37-induced endothelial cell activation,” International Journal of Molecular Medicine, vol. 22, no. 5, pp. 657–662, 2008.
[222]
B. Musicki, M. F. Kramer, R. E. Becker, and A. L. Burnett, “Inactivation of phosphorylated endothelial nitric oxide synthase (Ser-1177) by O-GlcNAc in diabetes-associated erectile dysfunction,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 33, pp. 11870–11875, 2005.
[223]
M. Federici, R. Menghini, A. Mauriello et al., “Insulin-dependent activation of endothelial nitric oxide synthase is impaired by O-linked glycosylation modification of signaling proteins in human coronary endothelial cells,” Circulation, vol. 106, no. 4, pp. 466–472, 2002.
[224]
X. L. Du, D. Edelstein, L. Rossetti et al., “Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 22, pp. 12222–12226, 2000.
[225]
Y. Q. Chen, M. Su, R. R. Walia, Q. Hao, J. W. Covington, and D. E. Vaughan, “Sp1 sites mediate activation of the plasminogen activator inhibitor-1 promoter by glucose in vascular smooth muscle cells,” Journal of Biological Chemistry, vol. 273, no. 14, pp. 8225–8231, 1998.
[226]
G. D. Holt and G. W. Hart, “The subcellular distribution of terminal N-acetylglucosamine moieties. Localization of a novel protein-saccharidie linkage, O-linked GlcNAc,” Journal of Biological Chemistry, vol. 261, no. 17, pp. 8049–8057, 1986.
[227]
P. J. Oates, “Aldose reductase, still a compelling target for diabetic neuropathy,” Current Drug Targets, vol. 9, no. 1, pp. 14–36, 2008.
[228]
S. K. Srivastava, U. C. S. Yadav, A. B. M. Reddy et al., “Aldose reductase inhibition suppresses oxidative stress-induced inflammatory disorders,” Chemico-Biological Interactions, vol. 191, no. 1–3, pp. 330–338, 2011.
[229]
P. Alexiou, K. Pegklidou, M. Chatzopoulou, I. Nicolaou, and V. J. Demopoulos, “Aldose reductase enzyme and its implication to major health problems of the 21st century,” Current Medicinal Chemistry, vol. 16, no. 6, pp. 734–752, 2009.
[230]
P. Geraldes and G. L. King, “Activation of protein kinase C isoforms and its impact on diabetic complications,” Circulation Research, vol. 106, no. 8, pp. 1319–1331, 2010.
[231]
M. E. Reyland, “Protein kinase C isoforms: multi-functional regulators of cell life and death,” Frontiers in Bioscience, vol. 14, no. 6, pp. 2386–2399, 2009.
[232]
X. Du, T. Matsumura, D. Edelstein et al., “Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells,” Journal of Clinical Investigation, vol. 112, no. 7, pp. 1049–1057, 2003.
[233]
V. Thallas-Bonke, S. R. Thorpe, M. T. Coughlan et al., “Inhibition of NADPH oxidase prevents advanced glycation end product-mediated damage in diabetic nephropathy through a protein kinase C-α-dependent pathway,” Diabetes, vol. 57, no. 2, pp. 460–469, 2008.
[234]
I. Fleming, B. Fisslthaler, S. Dimmeler, B. E. Kemp, and R. Busse, “Phosphorylation of Thr495 regulates Ca2+/calmodulin-dependent endothelial nitric oxide synthase activity,” Circulation research, vol. 88, no. 11, pp. E68–E75, 2001.
[235]
K. I. Hirata, R. Kuroda, T. Sakoda et al., “Inhibition of endothelial nitric oxide synthase activity by protein kinase C,” Hypertension, vol. 25, no. 2, pp. 180–185, 1995.
[236]
X. Jiang, F. Yang, H. Tan, et al., “Hyperhomocystinemia impairs endothelial function and eNOS activity via PKC activation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 12, pp. 2515–2521, 2005.
[237]
B. J. Michell, Z. P. Chen, T. Tiganis et al., “Coordinated control of endothelial nitric-oxide synthase phosphorylation by protein kinase C and the cAMP-dependent protein pinase,” Journal of Biological Chemistry, vol. 276, no. 21, pp. 17625–17628, 2001.
[238]
P. Nigro, J. I. Abe, C. H. Woo et al., “PKCζ decreases eNOS protein stability via inhibitory phosphorylation of ERK5,” Blood, vol. 116, no. 11, pp. 1971–1979, 2010.
[239]
R. Magid and P. F. Davies, “Endothelial protein kinase C isoform identity and differential activity of PKCζ in an athero-susceptible region of porcine aorta,” Circulation Research, vol. 97, no. 5, pp. 443–449, 2005.
[240]
I. Fleming, A. Mohamed, J. Galle et al., “Oxidized low-density lipoprotein increases superoxide production by endothelial nitric oxide synthase by inhibiting PKCα,” Cardiovascular Research, vol. 65, no. 4, pp. 897–906, 2005.
[241]
C. Partovian, Z. Zhuang, K. Moodie et al., “PKCα activates eNOS and increases arterial blood flow in vivo,” Circulation Research, vol. 97, no. 5, pp. 482–487, 2005.
[242]
N. S. Harhaj, E. A. Felinski, E. B. Wolpert, et al., “VEGF activation of protein kinase C stimulates occludin phosphorylation and contributes to endothelial permeability,” Investigative Ophthalmology and Visual Science, vol. 47, no. 11, pp. 5106–5115, 2006.
[243]
J. J. Lynch, T. J. Ferro, F. A. Blumenstock, A. M. Brockenauer, and A. B. Malik, “Increased endothelial albumin permeability mediated by protein kinase C activation,” Journal of Clinical Investigation, vol. 85, no. 6, pp. 1991–1998, 1990.
[244]
B. Williams, B. Gallacher, H. Patel, and C. Orme, “Glucose-induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro,” Diabetes, vol. 46, no. 9, pp. 1497–1503, 1997.
[245]
J. Y. Park, N. Takahara, A. Gabriele et al., “Induction of endothelin-1 expression by glucose an effect of protein kinase C activation,” Diabetes, vol. 49, no. 7, pp. 1239–1248, 2000.
[246]
R. D. Minshall, E. E Vandenbroucke, M. Holinstat, et al., “Role of protein kinase Czeta in thrombin-induced RhoA activation and inter-endothelial gap formation of human dermal microvessel endothelial cell monolayers,” Microvascular Research, vol. 80, no. 2, pp. 240–249, 2010.
[247]
A. Rahman, M. Bando, J. Kefer, K. N. Anwar, and A. B. Malik, “Protein kinase C-activated oxidant generation in endothelial cells signals intercellular adhesion molecule-1 gene transcription,” Molecular Pharmacology, vol. 55, no. 3, pp. 575–583, 1999.
[248]
J. I. Abe, “Role of PKCs and NF-κB activation in myocardial inflammation: enemy or ally?” Journal of Molecular and Cellular Cardiology, vol. 43, no. 4, pp. 404–408, 2007.
[249]
D. T. Bolick, S. Srinivasan, A. Whetzel, et al., “12/15 lipoxygenase mediates monocyte adhesion to aortic endothelium in apolipoprotein E-deficient mice through activation of RhoA and NF-κB,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, no. 6, pp. 1260–1266, 2006.
[250]
A. Kawakami, M. Aikawa, N. Nitta, et al., “Apolipoprotein CIII-induced THP-1 cell adhesion to endothelial cells involves pertussis toxin-sensitive G protein- and protein kinase C α-mediated nuclear factor-κB activation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 1, pp. 219–225, 2007.
[251]
T. Minami, R. M. Abid, J. Zhang, G. King, T. Kodama, and W. C. Aird, “Thrombin stimulation of vascular adhesion molecule-1 in endothelial cells is mediated by protein kinase C (PKC)-δ-NF-κB and PKC-ζ-GATA signaling pathways,” Journal of Biological Chemistry, vol. 278, no. 9, pp. 6976–6984, 2003.
[252]
A. Rahman, K. N. Anwar, S. Uddin et al., “Protein kinase C-δ regulates thrombin-induced ICAM-1 gene expression in endothelial cells via activation of p38 mitogen-activated protein kinase,” Molecular and Cellular Biology, vol. 21, no. 16, pp. 5554–5565, 2001.
[253]
A. Rahman, K. N. Anwar, and A. B. Malik, “Protein kinase C-ζ mediates TNF-α-induced ICAM-1 gene transcription in endothelial cells,” American Journal of Physiology—Cell Physiology, vol. 279, no. 4, pp. C906–C914, 2000.
[254]
U. Chakravarthy, R. G. Hayes, A. W. Stitt, E. McAuley, and D. B. Archer, “Constitutive nitric oxide synthase expression in retinal vascular endothelial cells is suppressed by high glucose and advanced glycation end products,” Diabetes, vol. 47, no. 6, pp. 945–952, 1998.
[255]
F. Cosentino, M. Eto, P. de Paolis et al., “High glucose causes upregulation of cyclooxygenase-2 and alters prostanoid profile in human endothelial cells: role of protein kinase C and reactive oxygen species,” Circulation, vol. 107, no. 7, pp. 1017–1023, 2003.
[256]
T. Inoguchi, P. Li, F. Umeda et al., “High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells,” Diabetes, vol. 49, no. 11, pp. 1939–1945, 2000.
[257]
A. Hempel, C. Maasch, U. Heintze et al., “High glucose concentrations increase endothelial cell permeability via activation of protein kinase C α,” Circulation Research, vol. 81, no. 3, pp. 363–371, 1997.
[258]
B. A. Wolf, J. R. Williamson, R. A. Easom, K. Chang, W. R. Sherman, and J. Turk, “Diacylglycerol accumulation and microvascular abnormalities induced by elevated glucose levels,” Journal of Clinical Investigation, vol. 87, no. 1, pp. 31–38, 1991.
[259]
N. Gaudreault, R. M. Perrin, M. Guo, et al., “Counter regulatory effects of PKCβII and PKCδ on coronary endothelial permeability,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 8, pp. 1527–1533, 2008.
[260]
G. M. Pieper and U. H. Riaz, “Activation of nuclear factor-κB in cultured endothelial cells by increased glucose concentration: prevention by calphostin C,” Journal of Cardiovascular Pharmacology, vol. 30, no. 4, pp. 528–532, 1997.
[261]
Y. Xu, S. Wang, L. Feng, Q. Zhu, P. Xiang, and B. He, “Blockade of PKC-β protects HUVEC from advanced glycation end products induced inflammation,” International Immunopharmacology, vol. 10, no. 12, pp. 1552–1559, 2010.
[262]
A. Kouroedov, M. Eto, H. Joch, M. Volpe, T. F. Lüscher, and F. Cosentino, “Selective inhibition of protein kinase Cβ2 prevents acute effects of high glucose on vascular cell adhesion molecule-1 expression in human endothelial cells,” Circulation, vol. 110, no. 1, pp. 91–96, 2004.
[263]
L. Quagliaro, L. Piconi, R. Assaloni, L. Martinelli, E. Motz, and A. Ceriello, “Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation,” Diabetes, vol. 52, no. 11, pp. 2795–2804, 2003.
[264]
T. Inoguchi, R. Battan, E. Handler, J. R. Sportsman, W. Heath, and G. L. King, “Preferential elevation of protein kinase C isoform βII and diacylglycerol levels in the aorta and heart of diabetic rats: differential reversibility to glycemic control by islet cell transplantation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 22, pp. 11059–11063, 1992.
[265]
N. Kang, G. Alexander, J. K. Park et al., “Differential expression of protein kinase C isoforms in streptozotocin- induced diabetic rats,” Kidney International, vol. 56, no. 5, pp. 1737–1750, 1999.
[266]
T. Shiba, T. Inoguchi, J. R. Sportsman, W. F. Heath, S. Bursell, and G. L. King, “Correlation of diacylglycerol level and protein kinase C activity in rat retina to retinal circulation,” American Journal of Physiology, vol. 265, no. 5, part 1, pp. E783–E793, 1993.
[267]
N. das Evcimen and G. L. King, “The role of protein kinase C activation and the vascular complications of diabetes,” Pharmacological Research, vol. 55, no. 6, pp. 498–510, 2007.
[268]
G. Booth, T. J. Stalker, A. M. Lefer, and R. Scalia, “Mechanisms of amelioration of glucose-induced endothelial dysfunction following inhibition of protein kinase C in vivo,” Diabetes, vol. 51, no. 5, pp. 1556–1564, 2002.
[269]
E. Harja, S. C. Jong, Y. Lu et al., “Mice deficient in PKCβ and apolipoprotein E display decreased atherosclerosis,” FASEB Journal, vol. 23, no. 4, pp. 1081–1091, 2009.
[270]
H. Ishii, M. R. Jirousek, D. Koya et al., “Amelioration of vascular dysfunctions in diabetic rats by an oral PKC β inhibitor,” Science, vol. 272, no. 5262, pp. 728–731, 1996.
[271]
M. R. Nangle, M. A. Cotter, and N. E. Cameron, “Protein kinase Cβ inhibition and aorta and corpus cavernosum function in streptozotocin-diabetic mice,” European Journal of Pharmacology, vol. 475, no. 1–3, pp. 99–106, 2003.
[272]
J. A. Beckman, A. B. Goldfine, M. B. Gordon, L. A. Garrett, and M. A. Creager, “Inhibition of protein kinase Cβ prevents impaired endothelium-dependent vasodilation caused by hyperglycemia in humans,” Circulation Research, vol. 90, no. 1, pp. 107–111, 2002.
[273]
N. N. Mehta, M. Sheetz, K. Price et al., “Selective PKC β inhibition with ruboxistaurin and endothelial function in type-2 diabetes mellitus,” Cardiovascular Drugs and Therapy, vol. 23, no. 1, pp. 17–24, 2009.
