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Cholesterol  2013 

HDL, Atherosclerosis, and Emerging Therapies

DOI: 10.1155/2013/891403

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Abstract:

This review aims to provide an overview on the properties of high-density lipoproteins (HDLs) and their cardioprotective effects. Emergent HDL therapies will be presented in the context of the current understanding of HDL function, metabolism, and protective antiatherosclerotic properties. The epidemiological association between levels of HDL-C or its major apolipoprotein (apoA-I) is strong, graded, and coherent across populations. HDL particles mediate cellular cholesterol efflux, have antioxidant properties, and modulate vascular inflammation and vasomotor function and thrombosis. A link of causality has been cast into doubt with Mendelian randomization data suggesting that genes causing HDL-C deficiency are not associated with increased cardiovascular risk, nor are genes associated with increased HDL-C, with a protective effect. Despite encouraging data from small studies, drugs that increase HDL-C levels have not shown an effect on major cardiovascular end-points in large-scale clinical trials. It is likely that the cholesterol mass within HDL particles is a poor biomarker of therapeutic efficacy. In the present review, we will focus on novel therapeutic avenues and potential biomarkers of HDL function. A better understanding of HDL antiatherogenic functions including reverse cholesterol transport, vascular protective and antioxidation effects will allow novel insight on novel, emergent therapies for cardiovascular prevention. 1. Introduction An increasing body of literature emphasizes the concept that HDL functionality, rather than the absolute cholesterol mass (HDL-C), may be a more accurate indicator for risk of developing atherosclerosis [1]. This hypothesis has led to investigation of HDL as both a biomarker for cardiovascular risk and a therapeutic target to be functionally modulated [2]. Epidemiological studies consistently demonstrate that low plasma level of HDL-C is associated with increased risk of CVD, but this epidemiological association has not translated into evidence that raising HDL-C prevents CVD. Atherosclerosis remains the leading cause of death in developed countries and is a major health concern worldwide. While LDL cholesterol (LDL-C) is clearly established as the major lipoprotein risk factor [3], the residual risk in large-scale clinical trials raises concern that other lipoprotein fractions may be causal in this residual risk. Increasingly, questions have been raised around the hypothesis that raising HDL-C pharmacologically is necessary beneficial. In this regard, after the recent failure of the drugs torcetrapib,

References

[1]  D. J. Rader and E. M. deGoma, “Approach to the patient with extremely low HDL-cholesterol,” The Journal of Clinical Endocrinology & Metabolism, vol. 97, no. 10, pp. 3399–3407, 2012.
[2]  D. J. Rader and A. R. Tall, “The not-so-simple HDL story: is it time to revise the HDL cholesterol hypothesis?” Nature Medicine, vol. 18, no. 9, pp. 1344–1346, 2012.
[3]  C. Baigent, L. Blackwell, J. Emberson, et al., “Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials,” The Lancet, vol. 376, no. 9753, pp. 1670–1681, 2010.
[4]  W. E. Boden, J. L. Probstfield, T. Anderson, et al., “Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy,” New England Journal of Medicine, vol. 365, no. 24, pp. 2255–2267, 2011.
[5]  R. S. Rosenson and A. M. Gotto Jr., “When clinical trials fail to address treatment gaps: the failure of niacin-laropiprant to reduce cardiovascular events,” Current Atherosclerosis Reports, vol. 15, no. 6, article 332, 2013.
[6]  C. Besler, K. Heinrich, L. Rohrer et al., “Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease,” Journal of Clinical Investigation, vol. 121, no. 7, pp. 2693–2708, 2011.
[7]  R. S. Rosenson, H. B. Brewer Jr., M. J. Chapman et al., “HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events,” Clinical Chemistry, vol. 57, no. 3, pp. 392–410, 2011.
[8]  E. J. Niesor, “Different effects of compounds decreasing cholesteryl ester transfer protein activity on lipoprotein metabolism,” Current Opinion in Lipidology, vol. 22, no. 4, pp. 288–295, 2011.
[9]  O. F. Delalla, H. A. Elliot, and J. W. Gofman, “Ultracentrifugal studies of high density serum lipoproteins in clinically healthy adults,” The American Journal of Physiology, vol. 179, no. 2, pp. 333–337, 1954.
[10]  J. C. Fruchart and J. M. Bard, “Lipoprotein particle measurement: an alternative approach to classification of lipid disorders,” Current Opinion in Lipidology, vol. 2, no. 6, pp. 362–366, 1991.
[11]  L. Camont, M. J. Chapman, and A. Kontush, “Biological activities of HDL subpopulations and their relevance to cardiovascular disease,” Trends in Molecular Medicine, vol. 17, no. 10, pp. 594–603, 2011.
[12]  J. W. Heinecke, “The HDL proteome: a marker—and perhaps mediator—of coronary artery disease,” Journal of Lipid Research, vol. 50, supplement, pp. S167–S171, 2009.
[13]  W. S. Davidson, R. A. G. D. Silva, S. Chantepie, W. R. Lagor, M. J. Chapman, and A. Kontush, “Proteomic analysis of defined hdl subpopulations reveals particle-specific protein clusters: relevance to antioxidative function,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 29, no. 6, pp. 870–876, 2009.
[14]  H. R. Superko, L. Pendyala, P. T. Williams, K. M. Momary, S. B. King III, and B. C. Garrett, “High-density lipoprotein subclasses and their relationship to cardiovascular disease,” Journal of Clinical Lipidology, vol. 6, no. 6, pp. 496–523, 2012.
[15]  A. V. Khera and D. J. Rader, “Future therapeutic directions in reverse cholesterol transport,” Current Atherosclerosis Reports, vol. 12, no. 1, pp. 73–81, 2010.
[16]  B. J. Ansell, M. Navab, S. Hama et al., “Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment,” Circulation, vol. 108, no. 22, pp. 2751–2756, 2003.
[17]  E. Di Angelantonio, N. Sarwar, P. Perry et al., “Major lipids, apolipoproteins, and risk of vascular disease,” Journal of the American Medical Association, vol. 302, no. 18, pp. 1993–2000, 2009.
[18]  R. H. Mackey, P. Greenland, D. C. Goff Jr., D. Lloyd-Jones, C. T. Sibley, and S. Mora, “High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events: MESA (multi-ethnic study of atherosclerosis),” Journal of the American College of Cardiology, vol. 60, no. 6, pp. 508–516, 2012.
[19]  H. N. Ginsberg, M. B. Elam, L. C. Lovato, et al., “Effects of combination lipid therapy in type 2 diabetes mellitus,” New England Journal of Medicine, vol. 362, no. 17, pp. 1563–1574, 2010.
[20]  M. Jun, C. Foote, J. Lv et al., “Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis,” The Lancet, vol. 375, no. 9729, pp. 1875–1884, 2010.
[21]  J. C. Fruchart, F. Sacks, M. P. Hermans et al., “The residual risk reduction initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia,” American Journal of Cardiology, vol. 102, no. 10, supplement, pp. 1K–34K, 2008.
[22]  B. J. Arsenault, P. Barter, D. A. DeMicco, et al., “TNT Study Investigators. Prediction of cardiovascular events in statin-treated stable coronary patients by lipid and nonlipid biomarkers,” Journal of the American College of Cardiology, vol. 57, no. 1, pp. 63–69, 2011.
[23]  W. A. van der Steeg, I. Holme, S. M. Boekholdt et al., “High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: significance for cardiovascular risk: the IDEAL and EPIC-Norfolk studies,” Journal of the American College of Cardiology, vol. 51, no. 6, pp. 634–642, 2008.
[24]  P. Barter, “Lessons Learned from the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) Trial,” American Journal of Cardiology, vol. 104, no. 10, 2009.
[25]  P. J. Barter, M. Caulfield, M. Eriksson, et al., “ILLUMINATE Investigators. Effects of torcetrapib in patients at high risk for coronary events,” New England Journal of Medicine, vol. 357, no. 21, pp. 2109–2122, 2007.
[26]  P. M. Ridker, J. Genest, S. M. Boekholdt et al., “HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial,” The Lancet, vol. 376, no. 9738, pp. 333–339, 2010.
[27]  G. G. Schwartz, A. G. Olsson, M. Abt, et al., “dal-OUTCOMES Investigators. Effects of dalcetrapib in patients with a recent acute coronary syndrome,” New England Journal of Medicine, vol. 367, no. 22, pp. 2089–2099, 2012.
[28]  HPS2-THRIVE Collaborative Group, “HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment,” European Heart Journal, vol. 34, no. 17, pp. 1279–1291, 2013.
[29]  C. Cook and C. Sheets, “Clinical equipoise and personal equipoise: two necessary ingredients for reducing bias in manual therapy trials,” Journal of Manual and Manipulative Therapy, vol. 19, no. 1, pp. 55–57, 2011.
[30]  R. Frikke-Schmidt, B. G. Nordestgaard, P. Schnohr, and A. Tybj?rg-Hansen, “Single nucleotide polymorphism in the low-density lipoprotein receptor is associated with a threefold risk of stroke: a case-control and prospective study,” European Heart Journal, vol. 25, no. 11, pp. 943–951, 2004.
[31]  B. F. Voight, G.M. Peloso, M. Orho-Melander, et al., “Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study,” The Lancet, vol. 380, no. 9841, pp. 572–580, 2012.
[32]  J. A. Glomset, “The plasma lecithins:cholesterol acyltransferase reaction,” Journal of Lipid Research, vol. 9, no. 2, pp. 155–167, 1968.
[33]  T. Devries-Seimon, Y. Li, M. Y. Pin et al., “Cholesterol-induced macrophage apoptosis requires ER stress pathways and engagement of the type A scavenger receptor,” Journal of Cell Biology, vol. 171, no. 1, pp. 61–73, 2005.
[34]  A. V. Khera, M. Cuchel, M. De La Llera-Moya et al., “Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis,” New England Journal of Medicine, vol. 364, no. 2, pp. 127–135, 2011.
[35]  H. H. Hassan, M. Denis, D. Y. D. Lee et al., “Identification of an ABCA1-dependent phospholipid-rich plasma membrane apolipoprotein A-I binding site for nascent HDL formation: implications for current models of HDL biogenesis,” Journal of Lipid Research, vol. 48, no. 11, pp. 2428–2442, 2007.
[36]  R. S. Rosenson, H. B. Brewer Jr., W. S. Davidson, et al., “Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport,” Circulation, vol. 125, no. 15, pp. 1905–1919, 2012.
[37]  G. H. Rothblat and M. C. Phillips, “High-density lipoprotein heterogeneity and function in reverse cholesterol transport,” Current Opinion in Lipidology, vol. 21, no. 3, pp. 229–238, 2010.
[38]  M. P. Adorni, F. Zimetti, J. T. Billheimer et al., “The roles of different pathways in the release of cholesterol from macrophages,” Journal of Lipid Research, vol. 48, no. 11, pp. 2453–2462, 2007.
[39]  J. F. Oram and A. M. Vaughan, “ABCA1-mediated transport of cellular cholesterol and phospholipids to HBL apolipoproteins,” Current Opinion in Lipidology, vol. 11, no. 3, pp. 253–260, 2000.
[40]  K. Nagao, M. Tomioka, and K. Ueda, “Function and regulation of ABCA1—membrane meso-domain organization and reorganization,” FEBS Journal, vol. 278, no. 18, pp. 3190–3203, 2011.
[41]  Y. Zhao, T. J. C. Van Berkel, and M. Van Eck, “Relative roles of various efflux pathways in net cholesterol efflux from macrophage foam cells in atherosclerotic lesions,” Current Opinion in Lipidology, vol. 21, no. 5, pp. 441–453, 2010.
[42]  M. G. Sorci-Thomas, J. S. Owen, B. Fulp, et al., “Nascent high density lipoproteins formed by ABCA1 resemble lipid rafts and are structurally organized by three apoA-I monomers,” Journal of Lipid Research, vol. 53, no. 9, pp. 1890–1909, 2012.
[43]  M. C. Phillips, “New insights into the determination of HDL structure by apolipoproteins,” Journal of Lipid Research, 2012.
[44]  K. Okuhira, M. L. Fitzgerald, N. Tamehiro et al., “Binding of PDZ-RhoGEF to ATP-binding cassette transporter A1 (ABCA1) induces cholesterol efflux through RhoA activation and prevention of transporter degradation,” Journal of Biological Chemistry, vol. 285, no. 21, pp. 16369–16377, 2010.
[45]  E. B. Neufeld, A. T. Remaley, S. J. Demosky et al., “Cellular localization and trafficking of the human ABCA1 transporter,” Journal of Biological Chemistry, vol. 276, no. 29, pp. 27584–27590, 2001.
[46]  G. Kellner-Weibel and M. de la Llera-Moya, “Update on HDL receptors and cellular cholesterol transport,” Current Atherosclerosis Reports, vol. 13, no. 3, pp. 233–241, 2011.
[47]  J. M. Timmins, J. Y. Lee, E. Boudyguina et al., “Targeted inactivation of hepatic Abca1 causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA-I,” Journal of Clinical Investigation, vol. 115, no. 5, pp. 1333–1342, 2005.
[48]  L. R. Brunham, J. K. Kruit, J. Iqbal et al., “Intestinal ABCA1 directly contributes to HDL biogenesis in vivo,” Journal of Clinical Investigation, vol. 116, no. 4, pp. 1052–1062, 2006.
[49]  Y. Zhang, F. C. McGillicuddy, C. C. Hinkle et al., “Adipocyte modulation of high-density lipoprotein cholesterol,” Circulation, vol. 121, no. 11, pp. 1347–1355, 2010.
[50]  C. Fernández-Hernando, Y. Suárez, K. J. Rayner, and K. J. Moore, “MicroRNAs in lipid metabolism,” Current Opinion in Lipidology, vol. 22, no. 2, pp. 86–92, 2011.
[51]  K. J. Rayner, F. J. Sheedy, C. C. Esau et al., “Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis,” Journal of Clinical Investigation, vol. 121, no. 7, pp. 2921–2931, 2011.
[52]  K. J. Rayner, C. C. Esau, F. N. Hussain, et al., “Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides,” Nature, vol. 478, no. 7369, pp. 404–407, 2011.
[53]  M. H. Oosterveer, A. Grefhorst, A. K. Groen, and F. Kuipers, “The liver X receptor: control of cellular lipid homeostasis and beyond: implications for drug design,” Progress in Lipid Research, vol. 49, no. 4, pp. 343–352, 2010.
[54]  M. De La Llera-Moya, D. Drazul-Schrader, B. F. Asztalos, M. Cuchel, D. J. Rader, and G. H. Rothblat, “The ability to promote efflux via ABCA1 determines the capacity of serum specimens with similar high-density lipoprotein cholesterol to remove cholesterol from macrophages,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 4, pp. 796–801, 2010.
[55]  T. E. Akiyama, S. Sakai, G. Lambert et al., “Conditional disruption of the peroxisome proliferator-activated receptor γ gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux,” Molecular and Cellular Biology, vol. 22, no. 8, pp. 2607–2619, 2002.
[56]  K. J. Rayner, Y. Su?rez, A. D?valos, et al., “MiR-33 contributes to the regulation of cholesterol homeostasis,” Science, vol. 328, no. 5985, pp. 1570–1573, 2010.
[57]  I. C. Gelissen, S. Cartland, A. J. Brown et al., “Expression and stability of two isoforms of ABCG1 in human vascular cells,” Atherosclerosis, vol. 208, no. 1, pp. 75–82, 2010.
[58]  I. D. Kerr, A. J. Haider, and I. C. Gelissen, “The ABCG family of membrane-associated transporters: you don't have to be big to be mighty,” British Journal of Pharmacology, vol. 164, no. 7, pp. 1767–1779, 2011.
[59]  E. J. Tarling, D. D. Bojanic, R. K. Tangirala et al., “Impaired development of atherosclerosis in Abcg1-/- Apoe -/- mice: identification of specific oxysterols that both accumulate in Abcg1-/- Apoe-/- tissues and induce apoptosis,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 6, pp. 1174–1180, 2010.
[60]  M. A. Kennedy, G. C. Barrera, K. Nakamura et al., “ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation,” Cell Metabolism, vol. 1, no. 2, pp. 121–131, 2005.
[61]  L. Yvan-Charvet, N. Wang, and A. R. Tall, “Role of HDL, ABCA1, and ABCG1 transporters in cholesterol efflux and immune responses,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 2, pp. 139–143, 2010.
[62]  M. Van Eck, I. S. T. Bos, R. B. Hildebrand, B. T. Van Rij, and T. J. C. Van Berkel, “Dual role for scavenger receptor class B, type I on bone marrow-derived cells in atherosclerotic lesion development,” American Journal of Pathology, vol. 165, no. 3, pp. 785–794, 2004.
[63]  E. Demetz, I. Tancevski, K. Duwensee, et al., “Inhibition of hepatic scavenger receptor-class B type I by RNA interference decreases atherosclerosis in rabbits,” Atherosclerosis, vol. 222, no. 2, pp. 360–366, 2012.
[64]  M. Vergeer, S. J. A. Korporaal, R. Franssen et al., “Genetic variant of the scavenger receptor BI in humans,” New England Journal of Medicine, vol. 364, no. 2, pp. 136–145, 2011.
[65]  A. Al-Jarallah and B. L. Trigatti, “A role for the scavenger receptor, class B type I in high density lipoprotein dependent activation of cellular signaling pathways,” Biochimica et Biophysica Acta, vol. 1801, no. 12, pp. 1239–1248, 2010.
[66]  X. Wang, H. L. Collins, M. Ranalletta et al., “Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo,” Journal of Clinical Investigation, vol. 117, no. 8, pp. 2216–2224, 2007.
[67]  R. B. Hildebrand, B. Lammers, I. Meurs et al., “Restoration of high-density lipoprotein levels by cholesteryl ester transfer protein expression in scavenger receptor class B Type i (SR-BI) knockout mice does not normalize pathologies associated with SR-BI deficiency,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 7, pp. 1439–1445, 2010.
[68]  M. El Bouhassani, S. Gilibert, M. Moreau et al., “Cholesteryl ester transfer protein expression partially attenuates the adverse effects of SR-BI receptor deficiency on cholesterol metabolism and atherosclerosis,” Journal of Biological Chemistry, vol. 286, no. 19, pp. 17227–17238, 2011.
[69]  D. Masson, M. Koseki, M. Ishibashi et al., “Increased HDL cholesterol and ApoA-I in humans and mice treated with a novel SR-BI inhibitor,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 29, no. 12, pp. 2054–2060, 2009.
[70]  M. Navab, S. T. Reddy, B. J. Van Lenten, and A. M. Fogelman, “HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms,” Nature Reviews Cardiology, vol. 8, no. 4, pp. 222–232, 2011.
[71]  C. Besler, T. F. Lüscher, and U. Landmesser, “Molecular mechanisms of vascular effects of High-density lipoprotein: alterations in cardiovascular disease,” EMBO Molecular Medicine, vol. 4, no. 4, pp. 251–268, 2012.
[72]  A. Kontush and M. J. Chapman, “Antiatherogenic function of HDL particle subpopulations: focus on antioxidative activities,” Current Opinion in Lipidology, vol. 21, no. 4, pp. 312–318, 2010.
[73]  S. A. Sorrentino, C. Besler, L. Rohrer et al., “Endothelial-vasoprotective effects of high-density lipoprotein are impaired in patients with type 2 diabetes mellitus but are improved after extended-release niacin therapy,” Circulation, vol. 121, no. 1, pp. 110–122, 2010.
[74]  M. Navab, S. Y. Hama, G. P. Hough, G. Subbanagounder, S. T. Reddy, and A. M. Fogelman, “A cell-free assay for detecting HDL that is dysfunctional in preventing the formation of or inactivating oxidized phospholipids,” Journal of Lipid Research, vol. 42, no. 8, pp. 1308–1317, 2001.
[75]  Y. Liu and C. Tang, “Regulation of ABCA1 functions by signaling pathways,” Biochimica et Biophysica Acta, vol. 1821, no. 3, pp. 522–529, 2012.
[76]  S. Patel, B. A. Di Bartolo, S. Nakhla et al., “Anti-inflammatory effects of apolipoprotein A-I in the rabbit,” Atherosclerosis, vol. 212, no. 2, pp. 392–397, 2010.
[77]  M. Riwanto, L. Rohrer, B. Roschitzki, et al., “Altered activation of endothelial anti- and proapoptotic pathways by high-density lipoprotein from patients with coronary artery disease: role of high-density lipoprotein-proteome remodeling,” Circulation, vol. 127, no. 8, pp. 891–904, 2013.
[78]  K. Sato and F. Okajima, “Role of sphingosine 1-phosphate in anti-atherogenic actions of high-density lipoprotein,” World Journal of Biological Chemistry, vol. 1, no. 11, pp. 327–337, 2010.
[79]  K. Alwaili, D. Bailey, Z. Awan, et al., “The HDL proteome in acute coronary syndromes shifts to an inflammatory profile,” Biochimica et Biophysica Acta, vol. 1821, no. 3, pp. 405–415, 2012.
[80]  C. Mineo, I. S. Yuhanna, M. J. Quon, and P. W. Shaul, “High density lipoprotein-induced endothelial nitric-oxide synthase activation is mediated by Akt and MAP kinases,” Journal of Biological Chemistry, vol. 278, no. 11, pp. 9142–9149, 2003.
[81]  I. Suc, I. Escargueil-Blanc, M. Troly, R. Salvayre, and A. Negre-Salvayre, “HDL and apoA prevent cell death of endothelial cells induced by oxidized LDL,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 17, no. 10, pp. 2158–2166, 1997.
[82]  T. Langmann, J. Klucken, M. Reil et al., “Molecular cloning of the human ATP-Binding cassette transporter 1 (hABC1): evidence for sterol-dependent regulation in macrophages,” Biochemical and Biophysical Research Communications, vol. 257, no. 1, pp. 29–33, 1999.
[83]  J. R. Nofer, M. F. Brodde, and B. E. Kehrel, “High-density lipoproteins, platelets and the pathogenesis of atherosclerosis: frontiers in research review: physiological and pathological functions of high-density lipoprotein,” Clinical and Experimental Pharmacology and Physiology, vol. 37, no. 7, pp. 726–735, 2010.
[84]  Y. Li, J. B. Dong, and M. P. Wu, “Human ApoA-I overexpression diminishes LPS-induced systemic inflammation and multiple organ damage in mice,” European Journal of Pharmacology, vol. 590, no. 1–3, pp. 417–422, 2008.
[85]  P. M. S. Figueirêdo, C. F. Catani, and T. Yano, “Serum high-density lipoprotein (HDL) inhibits in vitro enterohemolysin (EHly) activity produced by enteropathogenic Escherichia coli,” FEMS Immunology and Medical Microbiology, vol. 38, no. 1, pp. 53–57, 2003.
[86]  K. Yin, S. L. Tang, X. H. Yu, et al., “Apolipoprotein A-I inhibits LPS-induced atherosclerosis in ApoE-/- mice possibly via activated STAT3-mediated upregulation of tristetraprolin,” Acta Pharmacologica Sinica, 2013.
[87]  K. M. Hager and S. L. Hajduk, “Mechanism of resistance of African trypanosomes to cytotoxic human HDL,” Nature, vol. 385, no. 6619, pp. 823–826, 1997.
[88]  R. Krishna, M. S. Anderson, A. J. Bergman et al., “Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure in healthy individuals: two double-blind, randomised placebo-controlled phase I studies,” The Lancet, vol. 370, no. 9603, pp. 1907–1914, 2007.
[89]  M. J. Chapman, W. Le Goff, M. Guerin, and A. Kontush, “Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors,” European Heart Journal, vol. 31, no. 2, pp. 149–164, 2010.
[90]  C. P. Cannon, S. Shah, H. M. Dansky, et al., “Safety of anacetrapib in patients with or at high risk for coronary heart disease,” New England Journal of Medicine, vol. 363, no. 25, pp. 2406–2415, 2010.
[91]  B. Lauring, A. K. Taggart, J. R. Tata, et al., “Niacin lipid efficacy is independent of both the niacin receptor GPR109A and free fatty acid suppression,” Science Translational Medicine, vol. 4, no. 148, p. 148ra115, 2012.
[92]  Clinical trial.gov.REVEAL: Randomized Evaluation of the Effects of Anacetrapib through Lipid-modification, 2010, http://clinicaltrials.gov/ct2/show/NCT01252953.
[93]  S. J. Nicholls, H. B. Brewer, J. J. Kastelein, et al., “Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial,” Journal of the American Medical Association, vol. 306, no. 19, pp. 2099–2109, 2011.
[94]  http://clinicaltrials.gov/show/NCT01687998.
[95]  L. A. Carlson, “Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review,” Journal of Internal Medicine, vol. 258, no. 2, pp. 94–114, 2005.
[96]  A. S. Wierzbicki, “Niacin: the only vitamin that reduces cardiovascular events,” International Journal of Clinical Practice, vol. 65, no. 4, pp. 379–385, 2011.
[97]  “Clofibrate and niacin in coronary heart disease,” Journal of the American Medical Association, vol. 231, no. 4, pp. 360–381, 1975.
[98]  E. Bruckert, J. Labreuche, and P. Amarenco, “Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis,” Atherosclerosis, vol. 210, no. 2, pp. 353–361, 2010.
[99]  C. P. Cannon, “High-density lipoprotein cholesterol as the Holy Grail,” Journal of the American Medical Association, vol. 306, no. 19, pp. 2153–2155, 2011.
[100]  I. Gouni-Berthold and H. K. Berthold, “The role of Niacin in lipid-lowering treatment: are we aiming too high?” Current Pharmaceutical Design, vol. 19, no. 17, pp. 3094–3106, 2013.
[101]  H. K. Parson, H. Harati, D. Cooper, and A. I. Vinik, “The role of prostaglandin D2 and the autonomic nervous system on Niacin induced flushing,” Journal of Diabetes, vol. 5, no. 1, pp. 59–67, 2013.
[102]  H. E. Bays, A. Shah, Q. Dong, C. McCrary Sisk, and D. Maccubbin, “Extended-release niacin/laropiprant lipid-altering consistency across patient subgroups,” International Journal of Clinical Practice, vol. 65, no. 4, pp. 436–445, 2011.
[103]  http://www.arisaph.com/newsroom/press.php.
[104]  C. R. Sirtori, L. Calabresi, G. Franceschini et al., “Cardiovascular status of carriers of the apolipoprotein A-IMilano mutant: the limone sul garda study,” Circulation, vol. 103, no. 15, pp. 1949–1954, 2001.
[105]  S. E. Nissen, T. Tsunoda, E. M. Tuzcu et al., “Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial,” Journal of the American Medical Association, vol. 290, no. 17, pp. 2292–2300, 2003.
[106]  United States Securities and Exchange Commission filing, 2013, http://www.faqs.org/sec-filings/091224/MEDICINES-CO-DE_8-K.
[107]  J. C. Tardif, “Emerging high-density lipoprotein infusion therapies: fulfilling the promise of epidemiology?” Journal of Clinical Lipidology, vol. 4, no. 5, pp. 399–404, 2010.
[108]  B. Ibanez, C. Giannarelli, G. Cimmino, et al., “Recombinant HDL(Milano) exerts greater anti-inflammatory and plaque stabilizing properties than HDL(wild-type),” Atherosclerosis, vol. 220, no. 1, pp. 72–77, 2012.
[109]  R. Chenevard, D. Hürlimann, L. Spieker, et al., “Reconstituted HDL in acute coronary syndromes,” Cardiovascular Therapeutics, vol. 30, no. 2, pp. e51–e57, 2012.
[110]  “A single ascending dose study examining the safety and pharmacokinetic profile of reconstituted high density lipoprotein (CSL112) administered to patients. In: ClinicalTrials.gov. National Library of Medicine,” 2012, http://www.clinicaltrials.gov/ct2/show/NCT01499420.
[111]  R. Waksman, R. Torguson, K. M. Kent et al., “A first-in-man, randomized, placebo-controlled study to evaluate the safety and feasibility of autologous delipidated high-density lipoprotein plasma infusions in patients with acute coronary syndrome,” Journal of the American College of Cardiology, vol. 55, no. 24, pp. 2727–2735, 2010.
[112]  F. M. Sacks, L. L. Rudel, A. Conner et al., “Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo,” Journal of Lipid Research, vol. 50, no. 5, pp. 894–907, 2009.
[113]  G. M. Anantharamaiah, J. L. Jones, and C. G. Brouillette, “Studies of synthetic peptide analogs of the amphiphatic helix. Structure of complexes with dimyristoyl phosphatidylcholine,” Journal of Biological Chemistry, vol. 260, no. 18, pp. 10248–10255, 1985.
[114]  J. D. Smith, “Apolipoprotein A-I and its mimetics for the treatment of atherosclerosis,” Current Opinion in Investigational Drugs, vol. 11, no. 9, pp. 989–996, 2010.
[115]  G. Datta, M. Chaddha, S. Hama et al., “Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide,” Journal of Lipid Research, vol. 42, no. 7, pp. 1096–1104, 2001.
[116]  P. K. Shah and K. Y. Chyu, “Apolipoprotein A-I mimetic peptides: potential role in atherosclerosis management,” Trends in Cardiovascular Medicine, vol. 15, no. 8, pp. 291–296, 2005.
[117]  D. Weihrauch, H. Xu, Y. Shi, et al., “Effects of D-4F on vasodilation, oxidative stress, angiostatin, myocardial inflammation, and angiogenic potential in tight-skin mice,” American Journal of Physiology, vol. 293, pp. H1432–H1441, 2007.
[118]  L. T. Bloedon, R. Dunbar, D. Duffy et al., “Safety, pharmacokinetics, and pharmacodynamics of oral apoA-I mimetic peptide D-4F in high-risk cardiovascular patients,” Journal of Lipid Research, vol. 49, no. 6, pp. 1344–1352, 2008.
[119]  C. B. Sherman, S. J. Peterson, and W. H. Frishman, “Apolipoprotein A-I mimetic peptides: a potential new therapy for the prevention of atherosclerosis,” Cardiology in Review, vol. 18, no. 3, pp. 141–147, 2010.
[120]  M. Navab, I. Shechter, G. M. Anantharamaiah, S. T. Reddy, B. J. Van Lenten, and A. M. Fogelman, “Structure and function of HDL mimetics,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 2, pp. 164–168, 2010.
[121]  C. E. Watson, N. Weissbach, L. Kjems et al., “Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function,” Journal of Lipid Research, vol. 52, no. 2, pp. 361–373, 2011.
[122]  J. Ou, Z. Ou, D. W. Jones et al., “L-4F, an apolipoprotein A-1 mimetic, dramatically improves vasodilation in hypercholesterolemia and sickle cell disease,” Circulation, vol. 107, no. 18, pp. 2337–2341, 2003.
[123]  X. Chen, C. Burton, X. Song et al., “An apoa-I mimetic peptide increases LCAT activity in mice through increasing HDL concentration,” International Journal of Biological Sciences, vol. 5, no. 5, pp. 489–499, 2009.
[124]  M. Navab, S. T. Reddy, G. M. Anantharamaiah et al., “Intestine may be a major site of action for the apoA-I mimetic peptide 4F whether administered subcutaneously or orally,” Journal of Lipid Research, vol. 52, no. 6, pp. 1200–1210, 2011.
[125]  M. Navab, S. T. Reddy, G. M. Anantharamaiah, et al., “D-4F-mediated reduction in metabolites of arachidonic and linoleic acids in the small intestine is associated with decreased inflammation in lowdensity lipoprotein receptor-null mice,” Journal of Lipid Research, vol. 53, pp. 437–445, 2012.
[126]  A. T. Remaley, F. Thomas, J. A. Stonik et al., “Synthetic amphipathic helical peptides promote lipid efflux from cells by an ABCA1-dependent and an ABCA1-independent pathway,” Journal of Lipid Research, vol. 44, no. 4, pp. 828–836, 2003.
[127]  G. M. Anantharamaiah, V. K. Mishra, D. W. Garber et al., “Structural requirements for antioxidative and anti-inflammatory properties of apolipoprotein A-I mimetic peptides,” Journal of Lipid Research, vol. 48, no. 9, pp. 1915–1923, 2007.
[128]  A. Chattopadhyay, M. Navab, and G. Hough, “A novel approach to oral ApoA-I mimetic therapy,” Journal of Lipid Research, vol. 54, no. 4, pp. 995–1010, 2013.
[129]  S. Imaizumi, M. Navab, C. Morgantini, et al., “Dysfunctional high-density lipoprotein and the potential of apolipoprotein A-1 mimetic peptides to normalize the composition and function of lipoproteins,” Circulation Journal, vol. 75, no. 7, pp. 1533–1538, 2011.
[130]  F. Tabet, A. T. Remaley, A. I. Segaliny et al., “The 5A apolipoprotein A-I mimetic peptide displays antiinflammatory and antioxidant properties in vivo and in vitro,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 2, pp. 246–252, 2010.
[131]  E. Carballo-Jane, Z. Chen, E. O'Neill et al., “ApoA-I mimetic peptides promote pre-β HDL formation in vivo causing remodeling of HDL and triglyceride accumulation at higher dose,” Bioorganic and Medicinal Chemistry, vol. 18, no. 24, pp. 8669–8678, 2010.
[132]  Y. Zheng, A. B. Patel, V. Narayanaswami, G. L. Hura, B. Hang, and J. K. Bielicki, “HDL mimetic peptide ATI-5261 forms an oligomeric assembly in solution that dissociates to monomers upon dilution,” Biochemistry, vol. 50, no. 19, pp. 4068–4076, 2011.
[133]  J. K. Bielicki, H. Zhang, Y. Cortez et al., “A new HDL mimetic peptide that stimulates cellular cholesterol efflux with high efficiency greatly reduces atherosclerosis in mice,” Journal of Lipid Research, vol. 51, no. 6, pp. 1496–1503, 2010.
[134]  http://circ.ahajournals.org/cgi/content/meeting_abstract/120/18_MeetingAbstracts/S445-a.
[135]  A. C. Edmondson, R. J. Brown, S. Kathiresan, et al., “Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans,” The Journal of Clinical Investigation, vol. 119, no. 4, pp. 1042–1050, 2009.
[136]  K. O. Badellino, M. L. Wolfe, M. P. Reilly, and D. J. Rader, “Endothelial lipase concentrations are increased in metabolic syndrome and associated with coronary atherosclerosis,” PLoS Medicine, vol. 3, no. 2, article e22, 2006.
[137]  N. P. Tang, L. S. Wang, L. Yang et al., “Protective effect of an endothelial lipase gene variant on coronary artery disease in a Chinese population,” Journal of Lipid Research, vol. 49, no. 2, pp. 369–375, 2008.
[138]  T. Ishida, S. Choi, R. K. Kundu et al., “Endothelial lipase is a major determinant of HDL level,” Journal of Clinical Investigation, vol. 111, no. 3, pp. 347–355, 2003.
[139]  E. M. deGoma and D. J. Rader, “Novel HDL-directed pharmacotherapeutic strategies,” Nature Reviews Cardiology, vol. 8, no. 5, pp. 266–277, 2011.
[140]  R. J. Brown, W. R. Lagor, S. Sankaranaravanan et al., “Impact of combined deficiency of hepatic lipase and endothelial lipase on the metabolism of both high-density lipoproteins and apolipoprotein b-containing lipoproteins,” Circulation Research, vol. 107, no. 3, pp. 357–364, 2010.
[141]  K. B. Goodman, M. J. Bury, M. Cheung, et al., “Discovery of potent, selective sulfonylfuran urea endothelial lipase inhibitors,” Bioorganic & Medicinal Chemistry Letters, vol. 19, no. 1, pp. 27–30, 2009.
[142]  D. P. O'Connell, D. F. LeBlanc, D. Cromley, J. Billheimer, D. J. Rader, and W. W. Bachovchin, “Design and synthesis of boronic acid inhibitors of endothelial lipase,” Bioorganic & Medicinal Chemistry Letters, vol. 22, no. 3, pp. 1397–1401, 2012.
[143]  T. M. Teslovich, K. Musunuru, A. V. Smith et al., “Biological, clinical and population relevance of 95 loci for blood lipids,” Nature, vol. 466, no. 7307, pp. 707–713, 2010.
[144]  http://circ.ahajournals.org/cgi/content/meeting_abstract/120/18_MeetingAbstracts/S1175-b.
[145]  X. Rousset, B. Vaisman, B. Auerbach et al., “Effect of recombinant human lecithin cholesterol acyltransferase infusion on lipoprotein metabolism in mice,” Journal of Pharmacology and Experimental Therapeutics, vol. 335, no. 1, pp. 140–148, 2010.
[146]  X. Rousset, R. Shamburek, B. Vaisman, M. Amar, and A. T. Remaley, “Lecithin cholesterol acyltransferase: an anti- or pro-atherogenic factor?” Current Atherosclerosis Reports, vol. 13, no. 3, pp. 249–256, 2011.
[147]  S. Asada, M. Kuroda, Y. Aoyagi et al., “Ceiling culture-derived proliferative adipocytes retain high adipogenic potential suitable for use as a vehicle for gene transduction therapy,” American Journal of Physiology, vol. 301, no. 1, pp. C181–C185, 2011.
[148]  D. J. Rader, “Molecular regulation of HDL metabolism and function: implications for novel therapies,” Journal of Clinical Investigation, vol. 116, no. 12, pp. 3090–3100, 2006.
[149]  D. Bailey, R. Jahagirdar, A. Gordon et al., “RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo,” Journal of the American College of Cardiology, vol. 55, no. 23, pp. 2580–2589, 2010.
[150]  A. Gordon, R. Jahagirdar, J. Johannson, et al., “RVX-208 a small molecule that induces apolipoprotein A-I production progresses to phase Ib/IIa clinical trials,” in Proceedings of the American College of Cardiology Scientific Sessions, Orlando, Fla, USA, 2009.
[151]  S. J. Nicholls, A. Gordon, J. Johansson et al., “Efficacy and safety of a novel oral inducer of apolipoprotein A-I synthesis in statin-treated patients with stable coronary artery disease: a randomized controlled trial,” Journal of the American College of Cardiology, vol. 57, no. 9, pp. 1111–1119, 2011.
[152]  S. J. Nicholls, A. Gordon, J. Johannson, et al., “ApoA-I induction as a potential cardioprotective strategy: rationale for the SUSTAIN and ASSURE studies,” Cardiovascular Drugs and Therapy, vol. 26, no. 2, pp. 181–187, 2012.
[153]  P. K. Shah, “Atherosclerosis: targeting endogenous apo A-I-a new approach for raising HDL,” Nature Reviews Cardiology, vol. 8, no. 4, pp. 187–188, 2011.
[154]  G. Lo Sasso, S. Murzilli, L. Salvatore, et al., “Intestinal specific LXR activation stimulates reverse cholesterol transport and protects from atherosclerosis,” Cell Metabolism, vol. 12, no. 2, pp. 187–193, 2010.
[155]  T. Yasuda, D. Grillot, J. T. Billheimer et al., “Tissue-specific liver X receptor activation promotes macrophage reverse cholesterol transport in vivo,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 4, pp. 781–786, 2010.
[156]  C. Giannarelli, G. Cimmino, T. M. Connolly, et al., “Synergistic effect of liver X receptor activation and simvastatin on plaque regression and stabilization: an magnetic resonance imaging study in a model of advanced atherosclerosis,” European Heart Journal, vol. 33, no. 2, pp. 264–273, 2012.
[157]  D. Peng, R. A. Hiipakka, J. T. Xie et al., “A novel potent synthetic steroidal liver X receptor agonist lowers plasma cholesterol and triglycerides and reduces atherosclerosis in LDLR-/- mice,” British Journal of Pharmacology, vol. 162, no. 8, pp. 1792–1804, 2011.
[158]  E. Rigamonti, L. Helin, S. Lestavel et al., “Liver X receptor activation controls intracellular cholesterol trafficking and esterification in human macrophages,” Circulation Research, vol. 97, no. 7, pp. 682–689, 2005.
[159]  M. N. Bradley, C. Hong, M. Chen, et al., “Ligand activation of LXR beta reverses atherosclerosis and cellular cholesterol overload in mice lacking LXR alpha and apoE,” Journal of Clinical Investigation, vol. 117, no. 8, pp. 2337–2346, 2007.
[160]  E. M. Quinet, M. D. Basso, A. R. Halpern et al., “LXR ligand lowers LDL cholesterol in primates, is lipid neutral in hamster, and reduces atherosclerosis in mouse,” Journal of Lipid Research, vol. 50, no. 12, pp. 2358–2370, 2009.
[161]  A. Katz, C. Udata, E. Ott et al., “Safety, pharmacokinetics, and pharmacodynamics of single doses of lxr-623, a novel liver X-receptor agonist, in healthy participants,” Journal of Clinical Pharmacology, vol. 49, no. 6, pp. 643–649, 2009.
[162]  K. Griffett, L. A. Solt, B. E. El-Gendy, T. M. Kamenecka, and T. P. Burris, “A liver-selective LXR inverse agonist that suppresses hepatic steatosis,” ACS Chemical Biology, vol. 8, no. 3, pp. 559–567, 2012.
[163]  A. Mencarelli and S. Fiorucci, “FXR an emerging therapeutic target for the treatment of atherosclerosis,” Journal of Cellular and Molecular Medicine, vol. 14, no. 1-2, pp. 79–92, 2010.
[164]  E. Hambruch, S. Miyazaki-Anzai, U. Hahn, et al., “Synthetic farnesoid X receptor agonists induce high-density lipoprotein-mediated transhepatic cholesterol efflux in mice and monkeys and prevent atherosclerosis in cholesteryl ester transfer protein transgenic low-density lipoprotein receptor (-/-) mice,” Journal of Pharmacology and Experimental Therapeutics, vol. 343, no. 3, pp. 556–567, 2012.
[165]  S. Fiorucci, S. Cipriani, F. Baldelli, and A. Mencarelli, “Bile acid-activated receptors in the treatment of dyslipidemia and related disorders,” Progress in Lipid Research, vol. 49, no. 2, pp. 171–185, 2010.
[166]  F. A. Al-Allaf, C. Coutelle, S. N. Waddington, A. L. David, R. Harbottle, and M. Themis, “LDLR-Gene therapy for familial hypercholesterolaemia: problems, progress, and perspectives,” International Archives of Medicine, vol. 3, no. 1, article 36, 2010.
[167]  M. Grossman, D. J. Rader, D. W. M. Muller et al., “A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia,” Nature Medicine, vol. 1, no. 11, pp. 1148–1154, 1995.
[168]  A. S. Plump, C. J. Scott, and J. L. Breslow, “Human apolipoprotein A-I gene expression increases high density lipoprotein and suppresses atherosclerosis in the apolipoprotein E-deficient mouse,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 20, pp. 9607–9611, 1994.
[169]  N. Maeda, H. Li, D. Lee, P. Oliver, S. H. Quarfordt, and J. Osada, “Targeted disruption of the apolipoprotein C-III gene in mice results in hypotriglyceridemia and protection from postprandial hypertriglyceridemia,” Journal of Biological Chemistry, vol. 269, no. 38, pp. 23610–23616, 1994.
[170]  D. Gaudet, J. de Wal, K. Tremblay et al., “Review of the clinical development of alipogene tiparvovec gene therapy for lipoprotein lipase deficiency,” Atherosclerosis Supplements, vol. 11, no. 1, pp. 55–60, 2010.
[171]  D. Gaudet, J. Méthot, S. Déry, et al., “Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPL(S447X)) gene therapy for lipoprotein lipase deficiency: an open-label trial,” Gene Therapy, vol. 20, no. 4, pp. 361–369, 2013.
[172]  T. J. Marquart, R. M. Allen, D. S. Ory, and A. Baldán, “miR-33 links SREBP-2 induction to repression of sterol transporters,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, pp. 12228–12232, 2010.
[173]  T. Horie, K. Ono, M. Horiguchi et al., “MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 40, pp. 17321–17326, 2010.

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