All Title Author
Keywords Abstract


Impact of Exercise and Metabolic Disorders on Heat Shock Proteins and Vascular Inflammation

DOI: 10.1155/2012/836519

Full-Text   Cite this paper   Add to My Lib

Abstract:

Heat shock proteins (Hsp) play critical roles in the body’s self-defense under a variety of stresses, including heat shock, oxidative stress, radiation, and wounds, through the regulation of folding and functions of relevant cellular proteins. Exercise increases the levels of Hsp through elevated temperature, hormones, calcium fluxes, reactive oxygen species (ROS), or mechanical deformation of tissues. Isotonic contractions and endurance- type activities tend to increase Hsp60 and Hsp70. Eccentric muscle contractions lead to phosphorylation and translocation of Hsp25/27. Exercise-induced transient increases of Hsp inhibit the generation of inflammatory mediators and vascular inflammation. Metabolic disorders (hyperglycemia and dyslipidemia) are associated with type 1 diabetes (an autoimmune disease), type 2 diabetes (the common type of diabetes usually associated with obesity), and atherosclerotic cardiovascular disease. Metabolic disorders activate HSF/Hsp pathway, which was associated with oxidative stress, increased generation of inflammatory mediators, vascular inflammation, and cell injury. Knock down of heat shock factor-1 (HSF1) reduced the activation of key inflammatory mediators in vascular cells. Accumulating lines of evidence suggest that the activation of HSF/Hsp induced by exercise or metabolic disorders may play a dual role in inflammation. The benefits of exercise on inflammation and metabolism depend on the type, intensity, and duration of physical activity. 1. Introduction The stress response is a self-protective mechanism against environmental stresses which is mediated via a group of evolutionally conserved proteins, heat shock proteins (Hsp). Hsp regulate the conformation and functions of a large number of cellular proteins in order to protect the body from stress [1]. The expression of Hsp is mainly modulated by a common transcription factor, heat shock factor-1 (HSF1). The activity, translocation, and expression of HSF1 respond to environmental stresses, such as heat shock, wounds, oxidative stress, and radiation [2]. Exercise is associated with transient elevations of Hsp expression, body temperature, hormones, and oxidative stress, which may reduce inflammatory mediators [3]. Metabolic disorders in common chronic diseases (diabetes, metabolic syndrome, and atherosclerotic cardiovascular disease) are associated with a prolonged stress response as a consequence of oxidative stress, altered hormone levels, vascular inflammation, and cell injury [4]. Type 1 diabetes is a common autoimmune disease characterized by pancreatic -cell

References

[1]  M. E. Feder and G. E. Hofmann, “Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology,” Annual Review of Physiology, vol. 61, pp. 243–282, 1999.
[2]  K. A. Morano and D. J. Thiele, “Heat shock factor function and regulation in response to cellular stress, growth, and differentiation signals,” Gene Expression, vol. 7, no. 4–6, pp. 271–282, 1999.
[3]  M. Locke, E. G. Noble, and B. G. Atkinson, “Exercising mammals synthesize stress proteins,” American Journal of Physiology, vol. 258, no. 4, pp. C723–C729, 1990.
[4]  M. Rizzo, F. Cappello, R. Marfil et al., “Heat-shock protein 60?kDa and atherogenic dyslipidemia in patients with untreated mild periodontitis: a pilot study,” Cell Stress and Chaperones, vol. 17, pp. 399–407, 2012.
[5]  A. L. Notkins and A. Lernmark, “Autoimmune type 1 diabetes: resolved and unresolved issues,” Journal of Clinical Investigation, vol. 108, no. 9, pp. 1247–1252, 2001.
[6]  E. G. Noble, C. W. J. Melling, and K. J. Milne, “HSP, exercise and skeletal muscle,” in Heat Shock Proteins and Whole Body Physiology, A. A. A. Asea and B. K. Pedersen, Eds., Heat Shock Proteins, pp. 285–316, Springer Science+Business Media, Dordrecht, The Netherlands, 2010.
[7]  P. L. Moseley, “Heat shock proteins and the inflammatory response,” Annals of the New York Academy of Sciences, vol. 856, pp. 206–213, 1998.
[8]  J. Ellis, “Proteins as molecular chaperones,” Nature, vol. 328, no. 6129, pp. 378–379, 1987.
[9]  J. Fontana, D. Fulton, Y. Chen et al., “Domain mapping studies reveal that the M domain of hsp90 serves as a molecular scaffold to regulate Akt-dependent phosphorylation of endothelial nitric oxide synthase and NO release,” Circulation Research, vol. 90, no. 8, pp. 866–873, 2002.
[10]  A. P. Arrigo, “The cellular “networking” of mammalian Hsp27 and its functions in the control of protein folding, redox state and apoptosis,” Advances in Experimental Medicine and Biology, vol. 594, pp. 14–26, 2007.
[11]  M. García-Arguinzonis, T. Padró, R. Lugano, V. Llorente-Cortes, and L. Badimon, “Low-density lipoproteins induce heat shock protein 27 dephosphorylation, oligomerization, and subcellular relocalization in human vascular smooth muscle cells,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 6, pp. 1212–1219, 2010.
[12]  A. Lakshmikuttyamma, P. Selvakumar, and R. K. Sharma, “Interaction between heat shock protein 70?kDa and calcineurin in cardiovascular systems (review),” International Journal of Molecular Medicine, vol. 17, no. 3, pp. 419–423, 2006.
[13]  E. G. Noble, K. J. Milne, and C. W. J. Melling, “Heat shock proteins and exercise: a primer,” Applied Physiology, Nutrition and Metabolism, vol. 33, no. 5, pp. 1050–1075, 2008.
[14]  Q. Jones, T. S. Voegeli, G. Li, Y. Chen, and R. W. Currie, “Heat shock proteins protect against ischemia and inflammation through multiple mechanisms,” Inflammation and Allergy, vol. 10, no. 4, pp. 247–259, 2011.
[15]  A. M. Shields, G. S. Panayi, and V. M. Corrigall, “A new-age for biologic therapies: long-term drug-free therapy with BiP?” Frontiers in Immunology, vol. 3, article 17, 2012.
[16]  W. van Eden, R. Spiering, F. Broere, and Z. R. van der Zee, “A case of mistaken identity: HSPs are no DAMPs but DAMPERs,” Cell Stress and Chaperones, vol. 17, no. 3, pp. 281–292, 2012.
[17]  J. Radons and G. Multhoff, “Immunostimulatory functions of membrane-bound and exported heat shock protein 70,” Exercise Immunology Review, vol. 11, pp. 17–33, 2005.
[18]  H. H. Kampinga, J. Hageman, M. J. Vos et al., “Guidelines for the nomenclature of the human heat shock proteins,” Cell Stress and Chaperones, vol. 14, no. 1, pp. 105–111, 2009.
[19]  E. Christians, A. A. Davis, S. D. Thomas, and I. J. Benjamin, “Maternal effect of Hsf1 on reproductive success,” Nature, vol. 407, no. 6805, pp. 693–694, 2000.
[20]  K. D. Sarge, V. Zimarino, K. Holm, C. Wu, and R. I. Morimoto, “Cloning and characterization of two mouse heat shock factors with distinct inducible and constitutive DNA-binding ability,” Genes and Development, vol. 5, no. 10, pp. 1902–1911, 1991.
[21]  M. Rallu, M. T. Loones, Y. Lallemand, R. Morimoto, M. Morange, and V. Mezger, “Function and regulation of heat shock factor 2 during mouse embryogenesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 6, pp. 2392–2397, 1997.
[22]  M. Tanabe, N. Sasai, K. Nagata et al., “The mammalian HSF4 gene generates both an activator and a repressor of heat shock genes by alternative splicing,” Journal of Biological Chemistry, vol. 274, no. 39, pp. 27845–27856, 1999.
[23]  N. F. Mivechi, A. C. Koong, A. J. Giaccia, and G. M. Hahn, “Analysis of HSF-1 phosphorylation in A549 cells treated with a variety of stresses,” International Journal of Hyperthermia, vol. 10, no. 3, pp. 371–379, 1994.
[24]  W. Xia and R. Voellmy, “Hyperphosphorylation of heat shock transcription factor 1 is correlated with transcriptional competence and slow dissociation of active factor trimers,” Journal of Biological Chemistry, vol. 272, no. 7, pp. 4094–4102, 1997.
[25]  B. Chu, F. Soncin, B. D. Price, M. A. Stevenson, and S. K. Calderwood, “Sequential phosphorylation by mitogen-activated protein kinase and glycogen synthase kinase 3 represses transcriptional activation by heat shock factor-1,” Journal of Biological Chemistry, vol. 271, no. 48, pp. 30847–30857, 1996.
[26]  J. Kim, A. Nueda, Y. H. Meng, W. S. Dynan, and N. F. Mivechi, “Analysis of the phosphorylation of human heat shock transcription factor-1 by MAP kinase family members,” Journal of Cellular Biochemistry, vol. 67, no. 1, pp. 43–54, 1997.
[27]  R. Dai, W. Frejtag, B. He, Y. Zhang, and N. F. Mivechi, “c-Jun NH2-terminal kinase targeting and phosphorylation of heat shock factor-1 suppress its transcriptional activity,” Journal of Biological Chemistry, vol. 275, no. 24, pp. 18210–18218, 2000.
[28]  C. I. Holmberg, S. E. F. Tran, J. E. Eriksson, and L. Sistonen, “Multisite phosphorylation provides sophisticated regulation of transcription factors,” Trends in Biochemical Sciences, vol. 27, no. 12, pp. 619–627, 2002.
[29]  K. A. Morano and D. J. Klionsky, “Differential effects of compartment deacidification on the targeting of membrane and soluble proteins to the vacuole in yeast,” Journal of Cell Science, vol. 107, pp. 2813–2824, 1994.
[30]  S. Airaksinen, T. Jokilehto, C. M. I. R?bergh, and M. Nikinmaa, “Heat- and cold-inducible regulation of HSP70 expression in zebrafish ZF4 cells,” Comparative Biochemistry and Physiology B, vol. 136, no. 2, pp. 275–282, 2003.
[31]  B. Metzler, R. Abia, M. Ahmad et al., “Activation of heat shock transcription factor 1 in atherosclerosis,” American Journal of Pathology, vol. 162, no. 5, pp. 1669–1676, 2003.
[32]  P. A. Berberian, W. Myers, M. Tytell, V. Challa, and M. G. Bond, “Immunohistochemical localization of heat shock protein-70 in normal-appearing and atherosclerotic specimens of human arteries,” American Journal of Pathology, vol. 136, no. 1, pp. 71–80, 1990.
[33]  S. I. Nadeau and J. Landry, “Mechanisms of activation and regulation of the heat shock-sensitive signaling pathways,” Advances in Experimental Medicine and Biology, vol. 594, pp. 100–113, 2007.
[34]  R. I. Morimoto, “Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators,” Genes and Development, vol. 12, no. 24, pp. 3788–3796, 1998.
[35]  C. W. Melling, D. B. Thorp, and E. G. Noble, “Regulation of myocardial heat shock protein 70 gene expression following exercise,” Journal of Molecular and Cellular Cardiology, vol. 37, no. 4, pp. 847–855, 2004.
[36]  Z. Paroo and E. G. Noble, “Isoproterenol potentiates exercise-induction of Hsp70 in cardiac and skeletal muscle,” Cell Stress and Chaperones, vol. 4, no. 3, pp. 199–204, 1999.
[37]  J. D. Johnson, J. Campisi, C. M. Sharkey, S. L. Kennedy, M. Nickerson, and M. Fleshner, “Adrenergic receptors mediate stress-induced elevations in extracellular Hsp72,” Journal of Applied Physiology, vol. 99, no. 5, pp. 1789–1795, 2005.
[38]  C. W. J. Melling, D. B. Thorp, K. J. Milne, M. P. Krause, and E. G. Noble, “Exercise-mediated regulation of Hsp70 expression following aerobic exercise training,” American Journal of Physiology, vol. 293, no. 6, pp. H3692–H3698, 2007.
[39]  M. B. Harris and J. W. Starnes, “Effects of body temperature during exercise training on myocardial adaptations,” American Journal of Physiology, vol. 280, no. 5, pp. H2271–H2280, 2001.
[40]  K. J. Milne, D. B. Thorp, M. Krause, and E. G. Noble, “Core temperature is a greater influence than endogenous 17beta-estradiol on the exercise-induced accumulation of myocardial heat shock protein mRNA,” Canadian Journal of Physiology and Pharmacology, vol. 89, no. 11, pp. 855–860, 2011.
[41]  F. Reichsman, S. P. Scordilis, P. M. Clarkson, and W. J. Evans, “Muscle protein changes following eccentric exercise in humans,” European Journal of Applied Physiology and Occupational Physiology, vol. 62, no. 4, pp. 245–250, 1991.
[42]  A. Puntschart, M. Vogt, H. R. Widmer, H. Hoppeler, and R. Billeter, “Hsp70 expression in human skeletal muscle after exercise,” Acta Physiologica Scandinavica, vol. 157, no. 4, pp. 411–417, 1996.
[43]  P. N. Shek and R. J. Shephard, “Physical exercise as a human model of limited inflammatory response,” Canadian Journal of Physiology and Pharmacology, vol. 76, no. 5, pp. 589–597, 1998.
[44]  H. A. Demirel, S. K. Powers, H. Naito, and N. Tumer, “The effects of exercise duration on adrenal HSP72/73 induction in rats,” Acta Physiologica Scandinavica, vol. 167, no. 3, pp. 227–231, 1999.
[45]  K. J. Milne and E. G. Noble, “Exercise-induced elevation of HSP70 is intensity dependent,” Journal of Applied Physiology, vol. 93, no. 2, pp. 561–568, 2002.
[46]  E. Fehrenbach, A. M. Niess, K. Voelker, H. Northoff, and F. C. Mooren, “Exercise intensity and duration affect blood soluble HSP72,” International Journal of Sports Medicine, vol. 26, no. 7, pp. 552–557, 2005.
[47]  J. P. Morton, D. P. M. MacLaren, N. T. Cable et al., “Time course and differential responses of the major heat shock protein families in human skeletal muscle following acute nondamaging treadmill exercise,” Journal of Applied Physiology, vol. 101, no. 1, pp. 176–182, 2006.
[48]  T. J. Koh and J. Escobedo, “Cytoskeletal disruption and small heat shock protein translocation immediately after lengthening contractions,” American Journal of Physiology, vol. 286, no. 3, pp. C713–C722, 2004.
[49]  G. Paulsen, K. Vissing, J. M. Kalhovde et al., “Maximal eccentric exercise induces a rapid accumulation of small heat shock proteins on myofibrils and a delayed HSP70 response in humans,” American Journal of Physiology, vol. 293, no. 2, pp. R844–R853, 2007.
[50]  L. Bornman, C. M. L. Steinmann, G. S. Gericke, and B. S. Polla, “In vivo heat shock protects rat myocardial mitochondria,” Biochemical and Biophysical Research Communications, vol. 246, no. 3, pp. 836–840, 1998.
[51]  I. A. Sammut and J. C. Harrison, “Cardiac mitochondrial complex activity is enhanced by heat shock proteins,” Clinical and Experimental Pharmacology and Physiology, vol. 30, no. 1-2, pp. 110–115, 2003.
[52]  A. R. Tupling, A. O. Gramolini, T. A. Duhamel et al., “HSP70 binds to the fast-twitch skeletal muscle sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA1a) and prevents thermal inactivation,” Journal of Biological Chemistry, vol. 279, no. 50, pp. 52382–52389, 2004.
[53]  G. C. Melkani, A. Cammarato, and S. I. Bernstein, “αB-crystallin maintains skeletal muscle myosin enzymatic activity and prevents its aggregation under heat-shock stress,” Journal of Molecular Biology, vol. 358, no. 3, pp. 635–645, 2006.
[54]  I. Kurucz, A. Morva, A. Vaag et al., “Decreased expression of heat shock protein 72 in skeletal muscle of patients with type 2 diabetes correlates with insulin resistance,” Diabetes, vol. 51, no. 4, pp. 1102–1109, 2002.
[55]  J. Chung, A. K. Nguyen, D. C. Henstridge et al., “HSP72 protects against obesity-induced insulin resistance,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 5, pp. 1739–1744, 2008.
[56]  R. M. Tanguay, Y. Wu, and E. W. Khandjian, “Tissue-specific expression of heat shock proteins of the mouse in the absence of stress,” Developmental Genetics, vol. 14, no. 2, pp. 112–118, 1993.
[57]  D. A. Kelly, P. M. Tiidus, M. E. Houston, and E. G. Noble, “Effect of vitamin E deprivation and exercise training on induction of HSP70,” Journal of Applied Physiology, vol. 81, no. 6, pp. 2379–2385, 1996.
[58]  R. Hernando and R. Manso, “Muscle fibre stress in response to exercise. Synthesis, accumulation and isoform transitions of 70-kDa heat-shock proteins,” European Journal of Biochemistry, vol. 243, no. 1-2, pp. 460–467, 1997.
[59]  A. McArdle, D. Pattwell, A. Vasilaki, R. D. Griffiths, and M. J. Jackson, “Contractile activity-induced oxidative stress: cellular origin and adaptive responses,” American Journal of Physiology, vol. 280, no. 3, pp. C621–C627, 2001.
[60]  Z. Murlasits, R. G. Cutlip, K. B. Geronilla, K. M. K. Rao, W. F. Wonderlin, and S. E. Alway, “Resistance training increases heat shock protein levels in skeletal muscle of young and old rats,” Experimental Gerontology, vol. 41, no. 4, pp. 398–406, 2006.
[61]  A. R. Tupling, E. Bombardier, R. D. Stewart, C. Vigna, and A. E. Aqui, “Muscle fiber type-specific response of Hsp70 expression in human quadriceps following acute isometric exercise,” Journal of Applied Physiology, vol. 103, no. 6, pp. 2105–2111, 2007.
[62]  J. T. Silver, H. Kowalchuk, and E. G. Noble, “hsp70 mRNA temporal localization in rat skeletal myofibers and blood vessels post-exercise,” Cell Stress and Chaperones, vol. 17, no. 1, pp. 109–120, 2012.
[63]  D. E. R. Warburton, C. W. Nicol, and S. S. D. Bredin, “Health benefits of physical activity: the evidence,” Canadian Medical Association Journal, vol. 174, no. 6, pp. 801–809, 2006.
[64]  U. M. Kujala, “Evidence on the effects of exercise therapy in the treatment of chronic disease,” British Journal of Sports Medicine, vol. 43, no. 8, pp. 550–555, 2009.
[65]  B. K. Pedersen, “Exercise-induced myokines and their role in chronic diseases,” Brain, Behavior, and Immunity, vol. 25, no. 5, pp. 811–816, 2011.
[66]  S. N. Blair, Y. Cheng, and J. S. Holder, “Is physical activity or physical fitness more important in defining health benefits?” Medicine and Science in Sports and Exercise, vol. 33, supplement 6, pp. S379–S399, 2001.
[67]  I. M. Lee and P. J. Skerrett, “Physical activity and all-cause mortality: what is the dose-response relation?” Medicine and Science in Sports and Exercise, vol. 33, supplement 6, pp. S459–S471, 2001.
[68]  F. P. Leung, L. M. Yung, I. Laher, X. Yao, Z. Y. Chen, and Y. Huang, “Exercise, vascular wall and cardiovascular diseases: an update (part 1),” Sports Medicine, vol. 38, no. 12, pp. 1009–1024, 2008.
[69]  M. Y. Lai, I. Laher, X. Yao, Y. C. Zhen, Y. Huang, and P. L. Fung, “Exercise, vascular wall and cardiovascular diseases: an update (part 2),” Sports Medicine, vol. 39, no. 1, pp. 45–63, 2009.
[70]  D. J. Green, “Exercise training as vascular medicine: direct impacts on the vasculature in humans,” Exercise and Sport Sciences Reviews, vol. 37, no. 4, pp. 196–202, 2009.
[71]  J. Padilla, G. H. Simmons, S. B. Bender, A. A. Arce-Esquivel, J. J. Whyte, and M. H. Laughlin, “Vascular effects of exercise: endothelial adaptations beyond active muscle beds,” Physiology, vol. 26, no. 3, pp. 132–145, 2011.
[72]  D. J. Green, A. Spence, J. R. Halliwill, N. T. Cable, and D. H. J. Thijssen, “Exercise and vascular adaptation in asymptomatic humans,” Experimental Physiology, vol. 96, no. 2, pp. 57–70, 2011.
[73]  X. L. Wang, A. Fu, S. Raghavakaimal, and H. C. Lee, “Proteomic analysis of vascular endothelial cells in response to laminar shear stress,” Proteomics, vol. 7, no. 4, pp. 588–596, 2007.
[74]  M. H. Laughlin, S. C. Newcomer, and S. B. Bender, “Importance of hemodynamic forces as signals for exercise-induced changes in endothelial cell phenotype,” Journal of Applied Physiology, vol. 104, no. 3, pp. 588–600, 2008.
[75]  P. T. Katzmarzyk and S. A. Lear, “Physical activity for obese individuals: a systematic review of effects on chronic disease risk factors,” Obesity Reviews, vol. 13, no. 2, pp. 95–105, 2012.
[76]  E. S. Ford, “Does exercise reduce inflammation? Physical activity and C-reactive protein among U.S. adults,” Epidemiology, vol. 13, no. 5, pp. 561–568, 2002.
[77]  S. Mora, N. Cook, J. E. Buring, P. M. Ridker, and I. M. Lee, “Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms,” Circulation, vol. 116, no. 19, pp. 2110–2118, 2007.
[78]  N. P. Walsh, M. Gleeson, D. B. Pyne et al., “Position statement. Part two: maintaining immune health,” Exercise Immunology Review, vol. 17, pp. 6–63, 2011.
[79]  M. Gleeson, N. C. Bishop, D. J. Stensel, M. R. Lindley, S. S. Mastana, and M. A. Nimmo, “The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease,” Nature Reviews Immunology, vol. 11, no. 9, pp. 607–615, 2011.
[80]  A. Izadpanah, R. J. Barnard, A. J. Almeda et al., “A short-term diet and exercise intervention ameliorates inflammation and markers of metabolic health in overweight/obese children,” American Journal of Physiology, vol. 303, no. 4, pp. E542–E550, 2012.
[81]  T. Saetre, E. Enoksen, T. Lyberg et al., “Supervised exercise training reduces plasma levels of the endothelial inflammatory markers E-selectin and ICAM-1 in patients with peripheral arterial disease,” Angiology, vol. 62, no. 4, pp. 301–305, 2011.
[82]  K. L. Moreau, A. E. Silver, F. A. Dinenno, and D. R. Seals, “Habitual aerobic exercise is associated with smaller femoral artery intima-media thickness with age in healthy men and women,” European Journal of Cardiovascular Prevention and Rehabilitation, vol. 13, no. 5, pp. 805–811, 2006.
[83]  K. Pahkala, O. J. Heinonen, O. Simell et al., “Association of physical activity with vascular endothelial function and intima-media thickness,” Circulation, vol. 124, no. 18, pp. 1956–1963, 2011.
[84]  Y. H. Ding, Y. Ding, J. Li, D. A. Bessert, and J. A. Rafols, “Exercise pre-conditioning strengthens brain microvascular integrity in a rat stroke model,” Neurological Research, vol. 28, no. 2, pp. 184–189, 2006.
[85]  M. D. Van Bruggen, A. C. Hackney, R. G. McMurray, and K. S. Ondrak, “The relationship between serum and salivary cortisol levels in response to different intensities of exercise,” International Journal of Sports Physiology and Performance, vol. 6, no. 3, pp. 396–407, 2011.
[86]  A. E. Mendham, C. E. Donges, E. A. Liberts, and R. Duffield, “Effects of mode and intensity on the acute exercise-induced IL-6 and CRP responses in a sedentary, overweight population,” European Journal of Applied Physiology, vol. 111, no. 6, pp. 1035–1045, 2011.
[87]  J. P. R. Scott, C. Sale, J. P. Greeves, A. Casey, J. Dutton, and W. D. Fraser, “Effect of exercise intensity in the cytokine response to an acute bout of running,” Medicine & Science in Sports & Exercise, vol. 43, no. 12, pp. 2297–2306, 2011.
[88]  Y. Chen and R. W. Currie, “Small interfering RNA knocks down heat shock factor-1 (HSF-1) and exacerbates pro-inflammatory activation of NF-κB and AP-1 in vascular smooth muscle cells,” Cardiovascular Research, vol. 69, no. 1, pp. 66–75, 2006.
[89]  P. H. McCormick, G. Chen, S. Tierney, C. J. Kelly, and D. J. Bouchier-Hayes, “Clinically applicable thermal preconditioning attenuates leukocyte-endothelial interactions,” Journal of the American College of Surgeons, vol. 197, no. 1, pp. 71–78, 2003.
[90]  A. D. Johnson, P. A. Berberian, M. Tytell, and M. G. Bond, “Differential distribution of 70-kD heat shock proteins in atherosclerosis. Its potential role in arterial SMC survival,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 15, no. 1, pp. 27–36, 1995.
[91]  D. G. Neschis, S. D. Safford, P. N. Raghunath et al., “Thermal preconditioning before rat arterial balloon injury: limitation of injury and sustained reduction of intimal thickening,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 18, no. 1, pp. 120–126, 1998.
[92]  E. M. Connolly, C. J. Kelly, G. Chen et al., “Pharmacological induction of HSP27 attenuates intimal hyperplasia in vivo,” European Journal of Vascular and Endovascular Surgery, vol. 25, no. 1, pp. 40–47, 2003.
[93]  D. J. Tessier, P. Komalavilas, B. Liu et al., “Transduction of peptide analogs of the small heat shock-related protein HSP20 inhibits intimal hyperplasia,” Journal of Vascular Surgery, vol. 40, no. 1, pp. 106–114, 2004.
[94]  Y. Zheng, C. N. Im, and J. S. Seo, “Inhibitory effect of Hsp70 on angiotensin II-induced vascular smooth muscle cell hypertrophy,” Experimental and Molecular Medicine, vol. 38, no. 5, pp. 509–518, 2006.
[95]  L. Denes, Z. Bori, E. Csonka, L. Entz, and Z. Nagy, “Reverse regulation of endothelial cells and myointimal hyperplasia on cell proliferation by a heatshock protein-coinducer after hypoxia,” Stroke, vol. 39, no. 3, pp. 1022–1024, 2008.
[96]  E. Fehrenbach and H. Northoff, “Free radicals, exercise, apoptosis, and heat shock proteins,” Exercise Immunology Review, vol. 7, pp. 66–89, 2001.
[97]  J. L. Staib, J. C. Quindry, J. P. French, D. S. Criswell, and S. K. Powers, “Increased temperature, not cardiac load, activates heat shock transcription factor 1 and heat shock protein 72 expression in the heart,” American Journal of Physiology, vol. 292, no. 1, pp. R432–R439, 2007.
[98]  Y. Ogura, H. Naito, S. Akin et al., “Elevation of body temperature is an essential factor for exercise-increased extracellular heat shock protein 72 level in rat plasma,” American Journal of Physiology, vol. 294, no. 5, pp. R1600–R1607, 2008.
[99]  Z. Paroo, J. V. Haist, M. Karmazyn, and E. G. Noble, “Exercise improves postischemic cardiac function in males but not females: consequences of a novel sex-specific heat shock protein 70 response,” Circulation Research, vol. 90, no. 8, pp. 911–917, 2002.
[100]  M. Amrani, N. Latif, K. Morrison et al., “Relative induction of heat shock protein in coronary endothelial cells and cardiomyocytes: implications for myocardial protection,” Journal of Thoracic and Cardiovascular Surgery, vol. 115, no. 1, pp. 200–209, 1998.
[101]  J. P. Leger, F. M. Smith, and R. W. Currie, “Confocal microscopic localization of constitutive and heat shock-induced proteins HSP70 and HSP27 in the rat heart,” Circulation, vol. 102, no. 14, pp. 1703–1709, 2000.
[102]  E. Tarricone, C. Scapin, M. Vitadello et al., “Cellular distribution of Hsp70 expression in rat skeletal muscles. Effects of moderate exercise training and chronic hypoxia,” Cell Stress and Chaperones, vol. 13, no. 4, pp. 483–495, 2008.
[103]  K. I. Milne, S. Wolff, and E. G. Noble, “Myocardial accumulation and localization of the inducible 70-KDa heat chock protein, Hsp 70, following exercise,” Journal of Applied Physiology, vol. 113, no. 6, pp. 853–860, 2012.
[104]  J. J. Whyte and M. Harold Laughlin, “The effects of acute and chronic exercise on the vasculature,” Acta Physiologica, vol. 199, no. 4, pp. 441–450, 2010.
[105]  S. Li, R. S. Piotrowicz, E. G. Levin, Y. J. Shyy, and S. Chien, “Fluid shear stress induces the phosphorylation of small heat shock proteins in vascular endothelial cells,” American Journal of Physiology, vol. 271, no. 3, pp. C994–C1000, 1996.
[106]  G. García-Carde?a, R. Fan, V. Shah et al., “Dynamic activation of endothelial nitric oxide synthase by Hsp90,” Nature, vol. 392, no. 6678, pp. 821–824, 1998.
[107]  A. R. Brooks, P. I. Lelkes, and G. M. Rubanyi, “Gene expression profiling of human aortic endothelial cells exposed to disturbed flow and steady laminar flow,” Physiological Genomics, vol. 9, no. 1, pp. 27–41, 2002.
[108]  S. A. Loktionova and A. E. Kabakov, “Protein phosphatase inhibitors and heat preconditioning prevent Hsp27 dephosphorylation, F-actin disruption and deterioration of morphology in ATP-depleted endothelial cells,” FEBS Letters, vol. 433, no. 3, pp. 294–300, 1998.
[109]  W. Pipkin, J. A. Johnson, T. L. Creazzo, J. Burch, P. Komalavilas, and C. Brophy, “Localization, macromolecular associations, and function of the small heat shock-related protein HSP20 in rat heart,” Circulation, vol. 107, no. 3, pp. 469–476, 2003.
[110]  H. Jerius, D. R. Karolyi, J. S. Mondy et al., “Endothelial-dependent vasodilation is associated with increases in the phosphorylation of a small heat shock protein (HSP20),” Journal of Vascular Surgery, vol. 29, no. 4, pp. 678–684, 1999.
[111]  C. M. Rembold, D. B. Foster, J. D. Strauss, C. J. Wingard, and J. E. van Eyk, “cGMP-mediated phosphorylation of heat shock protein 20 may cause smooth muscle relaxation without myosin light chain dephosphorylation in swine carotid artery,” Journal of Physiology, vol. 524, no. 3, pp. 865–878, 2000.
[112]  E. C. McLemore, D. J. Tessier, C. R. Flynn et al., “Transducible recombinant small heat shock-related protein, HSP20, inhibits vasospasm and platelet aggregation,” Surgery, vol. 136, no. 3, pp. 573–578, 2004.
[113]  S. Salinthone, M. Tyagi, and W. T. Gerthoffer, “Small heat shock proteins in smooth muscle,” Pharmacology and Therapeutics, vol. 119, no. 1, pp. 44–54, 2008.
[114]  I. K. Kim, T. G. Park, Y. H. Kim, J. W. Cho, B. S. Kang, and C. Y. Kim, “Heat-shock response is associated with enhanced contractility of vascular smooth muscle in isolated rat aorta,” Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 369, no. 4, pp. 402–407, 2004.
[115]  K. A. Pritchard, A. W. Ackerman, E. R. Gross et al., “Heat shock protein 90 mediates the balance of nitric oxide and superoxide anion from endothelial nitric-oxide synthase,” Journal of Biological Chemistry, vol. 276, no. 21, pp. 17621–17624, 2001.
[116]  W. Insull Jr., “The pathology of atherosclerosis: plaque development and plaque responses to medical treatment,” American Journal of Medicine, vol. 122, supplement 1, pp. S3–S14, 2009.
[117]  M. Simionescu and F. Antohe, “Functional ultrastructure of the vascular endothelium: changes in various pathologies,” Handbook of Experimental Pharmacology, no. 176, pp. 41–69, 2006.
[118]  A. A. Arce-Esquivel, K. V. Kreutzer, J. W. Rush, J. R. Turk, and M. H. Laughlin, “Exercise does not attenuate early CAD progression in a pig model,” Medicine & Science in Sports & Exercise, vol. 44, no. 1, pp. 27–38, 2012.
[119]  D. P. Hajjar and M. E. Haberland, “Lipoprotein trafficking in vascular cells: molecular Trojan horses and cellular saboteurs,” Journal of Biological Chemistry, vol. 272, no. 37, pp. 22975–22978, 1997.
[120]  D. G. Harrison, J. Widder, I. Grumbach, W. Chen, M. Weber, and C. Searles, “Endothelial mechanotransduction, nitric oxide and vascular inflammation,” Journal of Internal Medicine, vol. 259, no. 4, pp. 351–363, 2006.
[121]  M. J. Crabtree, A. L. Tatham, Y. Al-Wakeel et al., “Quantitative regulation of intracellular endothelial nitric-oxide synthase (eNOS) coupling by both tetrahydrobiopterineNOS stoichiometry and biopterin redox status insights from cells with TET-regulated GTP cyclohydrolase I expression,” Journal of Biological Chemistry, vol. 284, no. 2, pp. 1136–1144, 2009.
[122]  J. S. Beckman, T. W. Beckman, J. Chen, P. A. Marshall, and B. A. Freeman, “Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 4, pp. 1620–1624, 1990.
[123]  A. Tedgui and Z. Mallat, “Anti-inflammatory mechanisms in the vascular wall,” Circulation Research, vol. 88, no. 9, pp. 877–887, 2001.
[124]  A. Kumar, Y. Takada, A. M. Boriek, and B. B. Aggarwal, “Nuclear factor-κB: its role in health and disease,” Journal of Molecular Medicine, vol. 82, no. 7, pp. 434–448, 2004.
[125]  B. Rinaldi, P. Romagnoli, S. Bacci et al., “Inflammatory events in a vascular remodeling model induced by surgical injury to the rat carotid artery,” British Journal of Pharmacology, vol. 147, no. 2, pp. 175–182, 2006.
[126]  S. L. DeMeester, T. G. Buchman, and J. P. Cobb, “The heat shock paradox: does NF-κB determine cell fate?” The FASEB Journal, vol. 15, no. 1, pp. 270–274, 2001.
[127]  U. Senftleben and M. Karin, “The IKK/NF-κB pathway,” Critical Care Medicine, vol. 30, supplement 1, pp. S18–S26, 2002.
[128]  R. Zhao and G. X. Shen, “Involvement of heat shock factor-1 in glycated LDL-induced upregulation of plasminogen activator inhibitor-1 in vascular endothelial cells,” Diabetes, vol. 56, no. 5, pp. 1436–1444, 2007.
[129]  G. Wick, R. Kleindienst, G. Schett, A. Amberger, and Q. Xu, “Role of heat shock protein 65/60 in the pathogenesis of atherosclerosis,” International Archives of Allergy and Immunology, vol. 107, no. 1–3, pp. 130–131, 1995.
[130]  Y. Chen, T. S. Voegeli, P. P. Liu, E. G. Noble, and R. W. Curie, “Heat stock paradox and a new role of heat shock proteins and their receptors as anti-inflammation targets,” Inflammation and Allergy, vol. 6, no. 2, pp. 91–100, 2007.
[131]  B. Henderson and A. G. Pockley, “Proteotoxic stress and circulating cell stress proteins in the cardiovascular diseases,” Cell Stress and Chaperones, vol. 17, no. 3, pp. 303–311, 2012.
[132]  M. Gleeson, N. C. Bishop, D. J. Stensel, M. R. Lindley, S. S. Mastana, and M. A. Nimmo, “The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease,” Nature Reviews Immunology, vol. 11, no. 9, pp. 607–615, 2011.
[133]  Y. Xie, C. Chen, M. A. Stevenson, D. A. Hume, P. E. Auron, and S. K. Calderwood, “NF-IL6 and HSF1 have mutually antagonistic effects on transcription in monocytic cells,” Biochemical and Biophysical Research Communications, vol. 291, no. 4, pp. 1071–1080, 2002.
[134]  T. Uchiyama, H. Atsuta, T. Utsugi et al., “HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function),” Atherosclerosis, vol. 190, no. 2, pp. 321–329, 2007.
[135]  A. K. De, K. M. Kodys, B. S. Yeh, and C. Miller-Graziano, “Exaggerated human monocyte IL-10 concomitant to minimal TNF-α induction by heat-shock protein 27 (Hsp27) suggests Hsp27 is primarily an antiinflammatory stimulus,” Journal of Immunology, vol. 165, no. 7, pp. 3951–3958, 2000.
[136]  L. Wieten, F. Broere, R. van der Zee, E. K. Koerkamp, J. Wagenaar, and W. van Eden, “Cell stress induced HSP are targets of regulatory T cells: a role for HSP inducing compounds as anti-inflammatory immuno-modulators?” FEBS Letters, vol. 581, no. 19, pp. 3716–3722, 2007.
[137]  C. M. Cahill, W. R. Waterman, Y. Xie, P. E. Auron, and S. K. Calderwood, “Transcriptional repression of the prointerleukin 1β gene by heat shock factor 1,” Journal of Biological Chemistry, vol. 271, no. 40, pp. 24874–24879, 1996.
[138]  I. Kim, H. M. Shin, and W. Baek, “Heat-shock response is associated with decreased production of interleukin-6 in murine aortic vascular smooth muscle cells,” Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 371, no. 1, pp. 27–33, 2005.
[139]  A. G. Pockley, S. K. Calderwood, and G. Multhoff, “The atheroprotective properties of Hsp70: a role for Hsp70-endothelial interactions?” Cell Stress and Chaperones, vol. 14, no. 6, pp. 545–553, 2009.
[140]  S. D. House and P. T. Guidon, “Effects of heat shock, stannous chloride, and gallium nitrate on the rat inflammatory response,” Cell Stress and Chaperones, vol. 6, no. 2, pp. 164–171, 2001.
[141]  N. Nakabe, S. Kokura, M. Shimozawa et al., “Hyperthermia attenuates TNF-alpha-induced up regulation of endothelial cell adhesion molecules in human arterial endothelial cells,” International Journal of Hyperthermia, vol. 23, no. 3, pp. 217–224, 2007.
[142]  P. Mehlen, C. Kretz-Remy, X. Préville, and A. P. Arrigo, “Human hsp27, Drosophila hsp27 and human αB-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFα-induced cell death,” The EMBO Journal, vol. 15, no. 11, pp. 2695–2706, 1996.
[143]  S. H. Baek, J. N. Min, E. M. Park et al., “Role of small heat shock protein HSP25 in radioresistance and glutathione-redox cycle,” Journal of Cellular Physiology, vol. 183, no. 1, pp. 100–107, 2000.
[144]  J. P. Gratton, J. Fontana, D. S. O'Connor, G. García-Carde?a, T. J. McCabe, and W. C. Sessa, “Reconstitution of an endothelial nitric-oxide synthase (eNOS), hsp90, and caveolin-1 complex in vitro: evidence that hsp90 facilitates calmodulin stimulated displacement of eNOS from caveolin-1,” Journal of Biological Chemistry, vol. 275, no. 29, pp. 22268–22272, 2000.
[145]  A. Brouet, P. Sonveaux, C. Dessy, J. L. Balligand, and O. Feron, “Hsp90 ensures the transition from the early Ca2+-dependent to the late phosphorylation-dependent activation of the endothelial nitric-oxide synthase in vascular endothelial growth factor-exposed endothelial cells,” Journal of Biological Chemistry, vol. 276, no. 35, pp. 32663–32669, 2001.
[146]  M. B. Harris, B. M. Mitchell, S. G. Sood, R. C. Webb, and R. C. Venema, “Increased nitric oxide synthase activity and Hsp90 association in skeletal muscle following chronic exercise,” European Journal of Applied Physiology, vol. 104, no. 5, pp. 795–802, 2008.
[147]  E. A. Kaperonis, C. D. Liapis, J. D. Kakisis, D. Dimitroulis, and V. G. Papavassiliou, “Inflammation and atherosclerosis,” European Journal of Vascular and Endovascular Surgery, vol. 31, no. 4, pp. 386–393, 2006.
[148]  C. Paul, F. Manero, S. Gonin, C. Kretz-Remy, S. Virot, and A. P. Arrigo, “Hsp27 as a negative regulator of cytochrome C release,” Molecular and Cellular Biology, vol. 22, no. 3, pp. 816–834, 2002.
[149]  V. L. Gabai, K. Mabuchi, D. D. Mosser, and M. Y. Sherman, “Hsp72 and stress kinase C-jun N-terminal kinase regulate the Bid-dependent pathway in tumor necrosis factor-induced apoptosis,” Molecular and Cellular Biology, vol. 22, no. 10, pp. 3415–3424, 2002.
[150]  J. M. Bruey, C. Ducasse, P. Bonniaud et al., “Hsp27 negatively regulates cell death by interacting with cytochrome C,” Nature Cell Biology, vol. 2, no. 9, pp. 645–652, 2000.
[151]  H. M. Beere, B. B. Wolf, K. Cain et al., “Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome,” Nature Cell Biology, vol. 2, no. 8, pp. 469–475, 2000.
[152]  L. Ravagnan, S. Gurbuxani, S. A. Susin et al., “Heat-shock protein 70 antagonizes apoptosis-inducing factor,” Nature Cell Biology, vol. 3, no. 9, pp. 839–843, 2001.
[153]  V. L. Gabai, A. B. Meriin, J. A. Yaglom, J. Y. Wei, D. D. Mosser, and M. Y. Sherman, “Suppression of stress kinase JNK is involved in HSP72-mediated protection of myogenic cells from transient energy deprivation. HSP72 alleviates the stress-induced inhibition of JNK dephosphorylation,” Journal of Biological Chemistry, vol. 275, no. 48, pp. 38088–38094, 2000.
[154]  P. Mehlen, K. Schulze-Osthoff, and A. P. Arrigo, “Small stress proteins as novel regulators of apoptosis. Heat shock protein 27 blocks Fas/APO-1- and staurosporine-induced cell death,” Journal of Biological Chemistry, vol. 271, no. 28, pp. 16510–16514, 1996.
[155]  N. J. Clemons, K. Buzzard, R. Steel, and R. L. Anderson, “Hsp72 inhibits Fas-mediated apoptosis upstream of the mitochondria in type II cells,” Journal of Biological Chemistry, vol. 280, no. 10, pp. 9005–9012, 2005.
[156]  K. J. Park, R. B. Gaynor, and Y. T. Kwak, “Heat shock protein 27 association with the IκB kinase complex regulates tumor necrosis factor α-induced NF-κB activation,” Journal of Biological Chemistry, vol. 278, no. 37, pp. 35272–35278, 2003.
[157]  Y. Chen, A. P. Arrigo, and R. W. Currie, “Heat shock treatment suppresses angiotensin II-induced activation of NF-κB pathway and heart inflammation: a role for IKK depletion by heat shock?” American Journal of Physiology, vol. 287, no. 3, pp. H1104–H1114, 2004.
[158]  Y. G. Weiss, Z. Bromberg, N. Raj et al., “Enhanced heat shock protein 70 expression alters proteasomal degradation of IκB kinase in experimental acute respiratory distress syndrome,” Critical Care Medicine, vol. 35, no. 9, pp. 2128–2138, 2007.
[159]  M. T. Schell, A. L. Spitzer, J. A. Johnson, D. Lee, and H. W. Harris, “Heat shock inhibits NF-κB activation in a dose- and time-dependent manner,” Journal of Surgical Research, vol. 129, no. 1, pp. 90–93, 2005.
[160]  M. der Perng, L. Cairns, P. van den IJssel, A. Prescott, A. M. Hutcheson, and R. A. Quinlan, “Intermediate filament interactions can be altered by HSP27 and αB-crystallin,” Journal of Cell Science, vol. 112, pp. 2099–2112, 1999.
[161]  H. Wei, W. Campbell, and R. S. van der Heide, “Heat shock-induced cardioprotection activates cytoskeletal-based cell survival pathways,” American Journal of Physiology, vol. 291, no. 2, pp. H638–H647, 2006.
[162]  J. Amour, A. K. Brzezinska, Z. Jager et al., “Hyperglycemia adversely modulates endothelial nitric oxide synthase during anesthetic preconditioning through tetrahydrobiopterin- and heat shock protein 90-mediated mechanisms,” Anesthesiology, vol. 112, pp. 576–585, 2010.
[163]  Y. Uchida, K. Takeshita, K. Yamamoto et al., “Stress augments insulin resistance and prothrombotic state: role of visceral adipose-derived monocyte chemoattractant protein-1,” Diabetes, vol. 61, pp. 1552–1561, 2012.
[164]  D. F. Pengiran Burut, A. Borai, C. Livingstone, and G. Ferns, “Serum heat shock protein 27 antigen and antibody levels appear to be related to the macrovascular complications associated with insulin resistance: a pilot study,” Cell Stress and Chaperones, vol. 15, no. 4, pp. 379–386, 2010.
[165]  Y. Huang, Y. Hu, W. Mai et al., “Plasma oxidized low-density lipoprotein is an independent risk factor in young patients with coronary artery disease,” Disease Markers, vol. 31, pp. 295–301, 2011.
[166]  S. Ren and G. X. Shen, “Impact of antioxidants and HDL on glycated LDL-induced generation of fibrinolytic regulators from vascular endothelial cells,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 20, no. 6, pp. 1688–1693, 2000.
[167]  G. Bellomo, E. Maggi, M. Poli, F. G. Agosta, P. Bollati, and G. Finardi, “Antoantibodies against oxidatively modified low-density lipoproteins in NIDDM,” Diabetes, vol. 44, no. 1, pp. 60–66, 1995.
[168]  R. Zhao, X. Ma, X. Xie, and G. X. Shen, “Involvement of NADPH oxidase in oxidized LDL-induced upregulation of heat shock factor-1 and plasminogen activator inhibitor-1 in vascular endothelial cells,” American Journal of Physiology, vol. 297, no. 1, pp. E104–E111, 2009.
[169]  S. C. Sharma, “Platelet adhesiveness, plasma fibrinogen and fibrinolytic activity in diabetes mellitus,” Thrombosis and Haemostasis, vol. 45, no. 1, article 100, 1981.
[170]  G. Pralong, T. Calandra, M. P. Glauser et al., “Plasminogen activator inhibitor 1: a new prognostic marker in septic shock,” Thrombosis and Haemostasis, vol. 61, no. 3, pp. 459–462, 1989.
[171]  X. Xu, H. Wang, Z. Wang, and W. Xiao, “Plasminogen activator inhibitor-1 promotes inflammatory process induced by cigarette smoke extraction or lipopolysaccharides in alveolar epithelial cells,” Experimental Lung Research, vol. 35, no. 9, pp. 795–805, 2009.
[172]  S. K. Roy Chowdhury, G. V. Sangle, X. Xie, G. L. Stelmack, A. J. Halayko, and G. X. Shen, “Effects of extensively oxidized low-density lipoprotein on mitochondrial function and reactive oxygen species in porcine aortic endothelial cells,” American Journal of Physiology, vol. 298, no. 1, pp. E89–E98, 2010.
[173]  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.
[174]  X. Xie, R. Zhao, and G. X. Shen, “Influence of delphinidin-3-glucoside on oxidized low density lipoprotein-indued oxidative stress and apoptosis in cultured endothelial cells,” Journal of Agricultural and Food Chemistry, vol. 60, pp. 1850–1856, 2012.
[175]  A. Rabinovitch, “Immunoregulatory and cytokine imbalances in the pathogenesis of IDDM: therapeutic intervention by immunostimulation?” Diabetes, vol. 43, no. 5, pp. 613–621, 1995.
[176]  M. D. S. Krause and P. I. de Bittencourt Jr., “Type 1 diabetes: can exercise impair the autoimmune event? The L-arginine/glutamine coupling hypothesis,” Cell Biochemistry and Function, vol. 26, no. 4, pp. 406–433, 2008.
[177]  A. P. Nácul, C. D. Andrade, P. Schwarz, P. I. H. de Bittencourt, and P. M. Spritzer, “Nitric oxide and fibrinogen in polycystic ovary syndrome: associations with insulin resistance and obesity,” European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 133, no. 2, pp. 191–196, 2007.
[178]  P. Newsholme, E. P. Haber, S. M. Hirabara et al., “Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity,” Journal of Physiology, vol. 583, no. 1, pp. 9–24, 2007.
[179]  J. E. Yardley, G. P. Kenny, B. A. Perkins et al., “Effects of performing resistance exercise before versus after aerobic exercise on glycemia in type 1 diabetes,” Diabetes Care, vol. 35, pp. 669–675, 2012.
[180]  M. Atalay, N. K. J. Oksala, D. E. Laaksonen et al., “Exercise training modulates heat shock protein response in diabetic rats,” Journal of Applied Physiology, vol. 97, no. 2, pp. 605–611, 2004.

Full-Text

comments powered by Disqus

Contact Us

service@oalib.com

QQ:3279437679

微信:OALib Journal