General Perspectives for the Treatment of Atherosclerosis

Page: [314 - 324] Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

Atherosclerosis, a cardiovascular disease, is at the top of the list among the diseases leading to death. Although the biochemical and pathophysiological cascades involved within the development of atherosclerosis have been identified clearly, its nature is quite complex to be treated with a single agent targeting a pathway. Therefore, many natural and synthetic compounds have been suggested for the treatment of the disease. The majority of the drugs employed target one of the single components of the pathological outcomes, resulting in many times less effective and longterm treatments. In most cases, treatment options prevent further worsening of the symptoms rather than a radical treatment. Consequently, the current review has been prepared to focus on the validated and non-validated targets of atherosclerosis as well as the alternative treatment options such as hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors, acyl-CoA cholesterol acyl transferase (ACAT) inhibitors, lipoprotein lipase stimulants, bile acid sequestrants, and some antioxidants. Related to the topic, both synthetic compounds designed employing medicinal chemistry skills and natural molecules becoming more popular in drug development are scrutinized in this mini review.

Keywords: Atherosclerosis, HMG-CoA reductase inhibitors, ACAT inhibitors, lipoprotein lipase stimulants, bile acid sequestrants, inflammation.

Graphical Abstract

[1]
Zhao, D.; Liu, J.; Wang, M.; Zhang, X.; Zhou, M. Epidemiology of cardiovascular disease in China: Current features and implications. Nat. Rev. Cardiol., 2019, 16(4), 203-212.
[http://dx.doi.org/10.1038/s41569-018-0119-4] [PMID: 30467329]
[2]
Taimur, S.D.M.; Nasrin, S.; Haq, M.M.; Gomes, H.I.; Islam, F. In hospital outcome of prediction of peripheral arterial disease in diabetic tobacco user patients. Anwer Khan Modern Med. Coll. J., 2018, 9, 102-109.
[http://dx.doi.org/10.3329/akmmcj.v9i2.39203]
[3]
Perales-Puchalt, J.; Vidoni, M.L.; Llibre Rodríguez, J.; Vidoni, E.D.; Billinger, S.; Burns, J.; Guerchet, M.; Lee, M. Cardiovascular health and dementia incidence among older adults in Latin America: Results from the 10/66 study. Int. J. Geriatr. Psychiatry, 2019, 34(7), 1041-1049.
[http://dx.doi.org/10.1002/gps.5107] [PMID: 30908765]
[4]
Gholipour, S.; Sewell, R.D.E.; Lorigooini, Z.; Rafieian-Kopaei, M. Medicinal plants and atherosclerosis: A review on molecular aspects. Curr. Pharm. Des., 2018, 24(26), 3123-3131.
[http://dx.doi.org/10.2174/1381612824666180911121525] [PMID: 30205790]
[5]
Escárcega, R.O.; Lipinski, M.J.; García-Carrasco, M.; Mendoza-Pinto, C.; Galvez-Romero, J.L.; Cervera, R. Inflammation and atherosclerosis: Cardiovascular evaluation in patients with autoimmune diseases. Autoimmun. Rev., 2018, 17(7), 703-708.
[http://dx.doi.org/10.1016/j.autrev.2018.01.021] [PMID: 29730525]
[6]
Pirillo, A.; Bonacina, F.; Norata, G.D.; Catapano, A.L. The interplay of lipids, lipoproteins, and immunity in atherosclerosis. Curr. Atheroscler. Rep., 2018, 20(3), 12.
[http://dx.doi.org/10.1007/s11883-018-0715-0] [PMID: 29445885]
[7]
Ross, R. The pathogenesis of atherosclerosis--an update. N. Engl. J. Med., 1986, 314(8), 488-500.
[http://dx.doi.org/10.1056/NEJM198602203140806] [PMID: 3511384]
[8]
Ross, R. Mechanisms of atherosclerosis--a review. Adv. Nephrol. Necker Hosp., 1990, 19, 79-86.
[PMID: 2105588]
[9]
Robbie, L.; Libby, P. Inflammation and atherothrombosis. Ann. N. Y. Acad. Sci., 2001, 947, 167-179.
[http://dx.doi.org/10.1111/j.1749-6632.2001.tb03939.x] [PMID: 11795264]
[10]
Kovanen, P.T. Mast cells: multipotent local effector cells in atherothrombosis. Immunol. Rev., 2007, 217, 105-122.
[http://dx.doi.org/10.1111/j.1600-065X.2007.00515.x] [PMID: 17498055]
[11]
Chambless, L.E.; Heiss, G.; Folsom, A.R.; Rosamond, W.; Szklo, M.; Sharrett, A.R.; Clegg, L.X. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993. Am. J. Epidemiol., 1997, 146(6), 483-494.
[http://dx.doi.org/10.1093/oxfordjournals.aje.a009302] [PMID: 9290509]
[12]
Berenson, G.S.; Srinivasan, S.R.; Bao, W.; Newman, W.P., III; Tracy, R.E.; Wattigney, W.A. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N. Engl. J. Med., 1998, 338(23), 1650-1656.
[http://dx.doi.org/10.1056/NEJM199806043382302] [PMID: 9614255]
[13]
Torres, N.; Guevara-Cruz, M.; Velázquez-Villegas, L.A.; Tovar, A.R. Nutrition and atherosclerosis. Arch. Med. Res., 2015, 46(5), 408-426.
[http://dx.doi.org/10.1016/j.arcmed.2015.05.010] [PMID: 26031780]
[14]
Burke, A.P.; Farb, A.; Virmani, R.; Goodin, J.; Smialek, J.E. Sports-related and non-sports-related sudden cardiac death in young adults. Am. Heart J., 1991, 121(2 Pt 1), 568-575.
[http://dx.doi.org/10.1016/0002-8703(91)90727-Y] [PMID: 1825009]
[15]
Nissen, S.E.; Tuzcu, E.M.; Schoenhagen, P.; Brown, B.G.; Ganz, P.; Vogel, R.A.; Crowe, T.; Howard, G.; Cooper, C.J.; Brodie, B.; Grines, C.L.; DeMaria, A.N. REVERSAL Investigators. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: A randomized controlled trial. JAMA, 2004, 291(9), 1071-1080.
[http://dx.doi.org/10.1001/jama.291.9.1071] [PMID: 14996776]
[16]
Navab, M.; Fogelman, A.M.; Berliner, J.A.; Territo, M.C.; Demer, L.L.; Frank, J.S.; Watson, A.D.; Edwards, P.A.; Lusis, A.J. Pathogenesis of atherosclerosis. Am. J. Cardiol., 1995, 76(9), 18C-23C.
[http://dx.doi.org/10.1016/S0002-9149(99)80466-4] [PMID: 7572682]
[17]
Imanaga, Y.; Sakata, N.; Takebayashi, S.; Matsunaga, A.; Sasaki, J.; Arakawa, K.; Nagai, R.; Horiuchi, S.; Itabe, H.; Takano, T. In vivo and in vitro evidence for the glycoxidation of low density lipoprotein in human atherosclerotic plaques. Atherosclerosis, 2000, 150(2), 343-355.
[http://dx.doi.org/10.1016/S0021-9150(99)00396-2] [PMID: 10856526]
[18]
Janoudi, A.; Shamoun, F.E.; Kalavakunta, J.K.; Abela, G.S. Cholesterol crystal induced arterial inflammation and destabilization of atherosclerotic plaque. Eur. Heart J., 2016, 37(25), 1959-1967.
[http://dx.doi.org/10.1093/eurheartj/ehv653] [PMID: 26705388]
[19]
Adams, C.W.M.; Bayliss, O.B. The relationship between diffuse intimal thickening, medial enzyme failure and intimal lipid deposition in various human arteries. J. Atheroscler. Res., 1969, 10(3), 327-339.
[http://dx.doi.org/10.1016/S0368-1319(69)80036-0] [PMID: 4243642]
[20]
Li, A.C.; Binder, C.J.; Gutierrez, A.; Brown, K.K.; Plotkin, C.R.; Pattison, J.W.; Valledor, A.F.; Davis, R.A.; Willson, T.M.; Witztum, J.L.; Palinski, W.; Glass, C.K. Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARalpha, β/δ, and γ. J. Clin. Invest., 2004, 114(11), 1564-1576.
[http://dx.doi.org/10.1172/JCI18730] [PMID: 15578089]
[21]
Fuster, V.; Stein, B.; Ambrose, J.A.; Badimon, L.; Badimon, J.J.; Chesebro, J.H. Atherosclerotic plaque rupture and thrombosis. Evolving concepts. Circulation, 1990, 82(3)(Suppl.), II47-II59.
[PMID: 2203564]
[22]
Fuster, V.; Steele, P.M.; Chesebro, J.H. Role of platelets and thrombosis in coronary atherosclerotic disease and sudden death. J. Am. Coll. Cardiol., 1985, 5(6)(Suppl.), 175B-184B.
[http://dx.doi.org/10.1016/S0735-1097(85)80552-0] [PMID: 3889109]
[23]
Ambrose, J.A.; Singh, M. Pathophysiology of coronary artery disease leading to acute coronary syndromes. F1000Prime Rep., 2015, 7, 08.
[http://dx.doi.org/10.12703/P7-08] [PMID: 25705391]
[24]
Bahmani, M.; Mirhoseini, M.; Shirzad, H.; Sedighi, M.; Shahinfard, N.; Rafieian-Kopaei, M. A review on promising natural agents effective on hyperlipidemia. J. Evid. Based Complementary Altern. Med., 2015, 20(3), 228-238.
[http://dx.doi.org/10.1177/2156587214568457] [PMID: 25633423]
[25]
Ross, R.; Harker, L. Hyperlipidemia and atherosclerosis. Science, 1976, 193(4258), 1094-1100.
[http://dx.doi.org/10.1126/science.822515] [PMID: 822515]
[26]
Heindel, J.J.; Blumberg, B.; Cave, M.; Machtinger, R.; Mantovani, A.; Mendez, M.A.; Nadal, A.; Palanza, P.; Panzica, G.; Sargis, R.; Vandenberg, L.N.; Vom Saal, F. Metabolism disrupting chemicals and metabolic disorders. Reprod. Toxicol., 2017, 68, 3-33.
[http://dx.doi.org/10.1016/j.reprotox.2016.10.001] [PMID: 27760374]
[27]
Zhou, X.; Zhang, W.; Liu, X.; Zhang, W.; Li, Y. Interrelationship between diabetes and periodontitis: Role of hyperlipidemia. Arch. Oral Biol., 2015, 60(4), 667-674.
[http://dx.doi.org/10.1016/j.archoralbio.2014.11.008] [PMID: 25443979]
[28]
Novák, J.; Olejníčková, V.; Tkáčová, N.; Santulli, G. Mechanistic role of microRNAs in coupling lipid metabolism and atherosclerosis. Adv. Exp. Med. Biol., 2015, 887, 79-100.
[http://dx.doi.org/10.1007/978-3-319-22380-3_5] [PMID: 26662987]
[29]
Aryal, B.; Singh, A.K.; Rotllan, N.; Price, N.; Fernández-Hernando, C. MicroRNAs and lipid metabolism. Curr. Opin. Lipidol., 2017, 28(3), 273-280.
[http://dx.doi.org/10.1097/MOL.0000000000000420] [PMID: 28333713]
[30]
Katsiki, N.; Mantzoros, C.; Mikhailidis, D.P. Adiponectin, lipids and atherosclerosis. Curr. Opin. Lipidol., 2017, 28(4), 347-354.
[http://dx.doi.org/10.1097/MOL.0000000000000431] [PMID: 28463859]
[31]
Gulcan, H.O.; Yigitkan, S.; Orhan, I.E. The natural products as hydroxymethylglutaryl-CoA reductase inhibitors. Lett. Drug Des. Disc., 2019, 16(10), 1130-1137.
[http://dx.doi.org/10.2174/1570180816666181112144353]
[32]
Istvan, E.S.; Deisenhofer, J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science, 2001, 292(5519), 1160-1164.
[http://dx.doi.org/10.1126/science.1059344] [PMID: 11349148]
[33]
Dimmeler, S.; Aicher, A.; Vasa, M.; Mildner-Rihm, C.; Adler, K.; Tiemann, M.; Rütten, H.; Fichtlscherer, S.; Martin, H.; Zeiher, A.M. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J. Clin. Invest., 2001, 108(3), 391-397.
[http://dx.doi.org/10.1172/JCI200113152] [PMID: 11489932]
[34]
Law, M.R.; Wald, N.J.; Rudnicka, A.R. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: Systematic review and meta-analysis. BMJ, 2003, 326(7404), 1423.
[http://dx.doi.org/10.1136/bmj.326.7404.1423] [PMID: 12829554]
[35]
Amarenco, P.; Labreuche, J. Lipid management in the prevention of stroke: Review and updated meta-analysis of statins for stroke prevention. Lancet Neurol., 2009, 8(5), 453-463.
[http://dx.doi.org/10.1016/S1474-4422(09)70058-4] [PMID: 19375663]
[36]
Endo, A. The origin of the statins. 2004. Atheroscler. Suppl., 2004, 5(3)(Suppl.), 125-130.
[http://dx.doi.org/10.1016/j.atherosclerosissup.2004.08.033] [PMID: 15531285]
[37]
Manzoni, M.; Rollini, M. Biosynthesis and biotechnological production of statins by filamentous fungi and application of these cholesterol-lowering drugs. Appl. Microbiol. Biotechnol., 2002, 58(5), 555-564.
[http://dx.doi.org/10.1007/s00253-002-0932-9] [PMID: 11956737]
[38]
Moorthy, N.H.H.; Cerqueira, N.M.; Ramos, M.J.; Fernandes, P.A. Ligand based analysis on HMG-CoA reductase inhibitors. Chemom. Intell. Lab. Syst., 2015, 140, 102-116.
[http://dx.doi.org/10.1016/j.chemolab.2014.11.009]
[39]
Hoffman, W.F.; Alberts, A.W.; Anderson, P.S.; Chen, J.S.; Smith, R.L.; Willard, A.K. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 4. Side chain ester derivatives of mevinolin. J. Med. Chem., 1986, 29(5), 849-852.
[http://dx.doi.org/10.1021/jm00155a040] [PMID: 3634830]
[40]
Corsini, A.; Maggi, F.M.; Catapano, A.L. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol. Res., 1995, 31(1), 9-27.
[http://dx.doi.org/10.1016/1043-6618(95)80042-5] [PMID: 7784310]
[41]
Endo, A. The discovery and development of HMG-CoA reductase inhibitors. J. Lipid Res., 1992, 33(11), 1569-1582.
[PMID: 1464741]
[42]
Leopoldini, M.; Malaj, N.; Toscano, M.; Sindona, G.; Russo, N. On the inhibitor effects of bergamot juice flavonoids binding to the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme. J. Agric. Food Chem., 2010, 58(19), 10768-10773.
[http://dx.doi.org/10.1021/jf102576j] [PMID: 20843083]
[43]
Di Donna, L.; Gallucci, G.; Malaj, N.; Romano, E.; Tagarelli, A.; Sindona, G. Recycling of industrial essential oil waste: brutieridin and melitidin, two anticholesterolaemic active principles from bergamot albedo. Food Chem., 2011, 125, 438-441.
[http://dx.doi.org/10.1016/j.foodchem.2010.09.025]
[44]
Babu, P.S.; Srinivasan, K. Hypolipidemic action of curcumin, the active principle of turmeric (Curcuma longa) in streptozotocin induced diabetic rats. Mol. Cell. Biochem., 1997, 166(1-2), 169-175.
[http://dx.doi.org/10.1023/A:1006819605211] [PMID: 9046034]
[45]
Lin, S.H.; Huang, K.J.; Weng, C.F.; Shiuan, D. Exploration of natural product ingredients as inhibitors of human HMG-CoA reductase through structure-based virtual screening. Drug Des. Devel. Ther., 2015, 9, 3313-3324.
[PMID: 26170618]
[46]
Thompson, P.D.; Panza, G.; Zaleski, A.; Taylor, B.; Taylor, B. Statin-associated side effects. J. Am. Coll. Cardiol., 2016, 67(20), 2395-2410.
[http://dx.doi.org/10.1016/j.jacc.2016.02.071] [PMID: 27199064]
[47]
Joseph, P.; Lonn, E.; Bosch, J.; Lopez, P.; Zhu, J.; Keltai, M. Dans, A.; Reid, C.; Khunti, K.; Toff, W.; Piegas, L.; Kim, J.H.; Swaminathan, B.; Bohm, M.; Yusuf, S. HOPE-3 Investigators. Long-term effects of statins, blood pressure-lowering, and both on erectile function in persons at intermediate risk for cardiovascular disease: A substudy of the Heart Outcomes Prevention Evaluation-3 (HOPE-3) randomized controlled trial. Can. J. Cardiol., 2018, 34(1), 38-44.
[http://dx.doi.org/10.1016/j.cjca.2017.09.026] [PMID: 29275880]
[48]
Rogers, M.A.; Liu, J.; Song, B.L.; Li, B.L.; Chang, C.C.; Chang, T.Y. Acyl-CoA:cholesterol acyltransferases (ACATs/SOATs): Enzymes with multiple sterols as substrates and as activators. J. Steroid Biochem. Mol. Biol., 2015, 151, 102-107.
[http://dx.doi.org/10.1016/j.jsbmb.2014.09.008] [PMID: 25218443]
[49]
Huang, L.H.; Melton, E.M.; Li, H.; Sohn, P.; Rogers, M.A.; Mulligan-Kehoe, M.J.; Fiering, S.N.; Hickey, W.F.; Chang, C.C.; Chang, T.Y. Myeloid acyl-CoA: Cholesterol acyltransferase 1 deficiency reduces lesion macrophage content and suppresses atherosclerosis progression. J. Biol. Chem., 2016, 291(12), 6232-6244.
[http://dx.doi.org/10.1074/jbc.M116.713818] [PMID: 26801614]
[50]
Kidani, Y.; Bensinger, S.J. Modulating cholesterol homeostasis to build a better T cell. Cell Metab., 2016, 23(6), 963-964.
[http://dx.doi.org/10.1016/j.cmet.2016.05.015] [PMID: 27304495]
[51]
Ohshiro, T.; Tomoda, H. Acyltransferase inhibitors: a patent review (2010-present). Expert Opin. Ther. Pat., 2015, 25(2), 145-158.
[http://dx.doi.org/10.1517/13543776.2014.989833] [PMID: 25470667]
[52]
Okopień, B.; Bułdak, Ł.; Bołdys, A. Current and future trends in the lipid lowering therapy. Pharmacol. Rep., 2016, 68(4), 737-747.
[http://dx.doi.org/10.1016/j.pharep.2016.03.016] [PMID: 27180022]
[53]
Rho, M.C.; Lee, H.S.; Lee, S.W.; Chang, J.S.; Kwon, O.E.; Chung, M.Y.; Kim, Y.K. Polyacetylenic compounds, ACAT inhibitors from the roots of Panax ginseng. J. Agric. Food Chem., 2005, 53(4), 919-922.
[http://dx.doi.org/10.1021/jf040370x] [PMID: 15712998]
[54]
Matsuda, K. ACAT inhibitors as antiatherosclerotic agents: Compounds and mechanisms. Med. Res. Rev., 1994, 14(3), 271-305.
[http://dx.doi.org/10.1002/med.2610140302] [PMID: 8007738]
[55]
Cryer, A. Tissue lipoprotein lipase activity and its action in lipoprotein metabolism. Int. J. Biochem., 1981, 13(5), 525-541.
[http://dx.doi.org/10.1016/0020-711X(81)90177-4] [PMID: 7016622]
[56]
Reimund, M.; Kovrov, O.; Olivecrona, G.; Lookene, A. Lipoprotein lipase activity and interactions studied in human plasma by isothermal titration calorimetry. J. Lipid Res., 2017, 58(1), 279-288.
[http://dx.doi.org/10.1194/jlr.D071787] [PMID: 27845686]
[57]
Kersten, S.; Stienstra, R. The role and regulation of the peroxisome proliferator activated receptor alpha in human liver. Biochimie, 2017, 136, 75-84.
[http://dx.doi.org/10.1016/j.biochi.2016.12.019] [PMID: 28077274]
[58]
Li, G.; Brocker, C.N.; Xie, C.; Yan, T.; Noguchi, A.; Krausz, K.W.; Xiang, R.; Gonzalez, F.J. Hepatic peroxisome proliferator-activated receptor alpha mediates the major metabolic effects of Wy-14643. J. Gastroenterol. Hepatol., 2018, 33(5), 1138-1145.
[http://dx.doi.org/10.1111/jgh.14046] [PMID: 29141109]
[59]
Ghonem, N.S.; Assis, D.N.; Boyer, J.L. Fibrates and cholestasis. Hepatology, 2015, 62(2), 635-643.
[http://dx.doi.org/10.1002/hep.27744] [PMID: 25678132]
[60]
Mottl, A.K.; Buse, J.B.; Ismail-Beigi, F.; Sigal, R.J.; Pedley, C.F.; Papademetriou, V.; Simmons, D.L.; Katz, L.; Mychaleckyj, J.C.; Craven, T.E. Long-term effects of intensive glycemic and blood pressure control and fenofibrate use on kidney outcomes. Clin. J. Am. Soc. Nephrol., 2018, 13(11), 1693-1702.
[http://dx.doi.org/10.2215/CJN.06200518] [PMID: 30361335]
[61]
Elam, M.B.; Ginsberg, H.N.; Lovato, L.C.; Corson, M.; Largay, J.; Leiter, L.A.; Lopez, C.; O’Connor, P.J.; Sweeney, M.E.; Weiss, D.; Friedewald, W.T.; Buse, J.B.; Gerstein, H.C.; Probstfield, J.; Grimm, R.; Ismail-Beigi, F.; Goff, D.C., Jr; Fleg, J.L.; Rosenberg, Y.; Byington, R.P. ACCORDION Study Investigators. Jr. Goff, D.C.; Fleg, J.L.; Rosenberg, Y.; Byington, R.P. Association of fenofibrate therapy with long-term cardiovascular risk in statin-treated patients with type 2 diabetes. JAMA Cardiol., 2017, 2(4), 370-380.
[http://dx.doi.org/10.1001/jamacardio.2016.4828] [PMID: 28030716]
[62]
Keech, A.; Simes, R.J.; Barter, P.; Best, J.; Scott, R.; Taskinen, M.R.; Forder, P.; Pillai, A.; Davis, T.; Glasziou, P.; Drury, P.; Kesäniemi, Y.A.; Sullivan, D.; Hunt, D.; Colman, P.; d’Emden, M.; Whiting, M.; Ehnholm, C.; Laakso, M. FIELD study investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): Randomised controlled trial. Lancet, 2005, 366(9500), 1849-1861.
[http://dx.doi.org/10.1016/S0140-6736(05)67667-2] [PMID: 16310551]
[63]
Maltarollo, V.G.; Togashi, M.; Nascimento, A.S.; Honorio, K.M. Structure-based virtual screening and discovery of New PPARδ/γ dual agonist and PPARδ and γ agonists. PLoS One, 2015, 10(3), e0118790.
[http://dx.doi.org/10.1371/journal.pone.0118790] [PMID: 25767888]
[64]
Giacoman-Martínez, A.; Alarcón-Aguilar, F.J.; Zamilpa, A.; Hidalgo-Figueroa, S.; Navarrete-Vázquez, G.; García-Macedo, R.; Román-Ramos, R.; Almanza-Pérez, J.C. Almanza-Pérez, J.C. Triterpenoids from Hibiscus sabdariffa L. with PPARδ/γ dual agonist action: in vivo, in vitro and in silico studies. Planta Med., 2019, 85(5), 412-423.
[http://dx.doi.org/10.1055/a-0824-1316] [PMID: 30650453]
[65]
Piemontese, L.; Cerchia, C.; Laghezza, A.; Ziccardi, P.; Sblano, S.; Tortorella, P.; Iacobazzi, V.; Infantino, V.; Convertini, P.; Dal Piaz, F.; Lupo, A.; Colantuoni, V.; Lavecchia, A.; Loiodice, F. New diphenylmethane derivatives as peroxisome proliferator-activated receptor alpha/gamma dual agonists endowed with anti-proliferative effects and mitochondrial activity. Eur. J. Med. Chem., 2017, 127, 379-397.
[http://dx.doi.org/10.1016/j.ejmech.2016.12.047] [PMID: 28076827]
[66]
Li, T.; Chiang, J.Y. Bile acids as metabolic regulators. Curr. Opin. Gastroenterol., 2015, 31(2), 159-165.
[http://dx.doi.org/10.1097/MOG.0000000000000156] [PMID: 25584736]
[67]
Ross, S.; D’Mello, M.; Anand, S.S.; Eikelboom, J.; Stewart, A.F.; Samani, N.J.; Roberts, R.; Paré, G. CARDIoGRAMplusC4D Consortium. Effect of bile acid sequestrants on the risk of cardiovascular events: A Mendelian randomization analysis. Circ Cardiovasc Genet, 2015, 8(4), 618-627.
[http://dx.doi.org/10.1161/CIRCGENETICS.114.000952] [PMID: 26043746]
[68]
Silverman, M.G.; Ference, B.A. Im, K.; Wiviott, S.D.; Giugliano, R.P.; Grundy, S.M.; Braunwald, E.; Sabatine, M.S. Im, K.; Wiviott, S.D.; Giugliano, R.P.; Grundy, S.M.; Sabatine, M.S. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: A systematic review and meta-analysis. JAMA, 2016, 316(12), 1289-1297.
[http://dx.doi.org/10.1001/jama.2016.13985] [PMID: 27673306]
[69]
Sandhu, S.; Moosavi, M.; Golmohammadi, K.; Francis, G.A. Colesevelam as an add-on treatment for control of dyslipidemia and hyperglycemia in type 2 diabetes. Can. J. Diabetes, 2016, 40(2), 112-114.
[http://dx.doi.org/10.1016/j.jcjd.2015.07.008] [PMID: 26584788]
[70]
Heřmánková, E.; Žák, A.; Poláková, L.; Hobzová, R.; Hromádka, R.; Širc, J. Polymeric bile acid sequestrants: Review of design, in vitro binding activities, and hypocholesterolemic effects. Eur. J. Med. Chem., 2018, 144, 300-317.
[http://dx.doi.org/10.1016/j.ejmech.2017.12.015] [PMID: 29275230]
[71]
Hou, R.; Goldberg, A.C. Lowering low-density lipoprotein cholesterol: Statins, ezetimibe, bile acid sequestrants, and combinations: Comparative efficacy and safety. Endocrinol. Metab. Clin. North Am., 2009, 38(1), 79-97.
[http://dx.doi.org/10.1016/j.ecl.2008.11.007] [PMID: 19217513]
[72]
Fleg, J.L.; Mete, M.; Howard, B.V.; Umans, J.G.; Roman, M.J.; Ratner, R.E.; Silverman, A.; Galloway, J.M.; Henderson, J.A.; Weir, M.R.; Wilson, C.; Stylianou, M.; Howard, W.J. Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in type 2 diabetes: The SANDS (Stop Atherosclerosis in Native Diabetics Study) trial. J. Am. Coll. Cardiol., 2008, 52(25), 2198-2205.
[http://dx.doi.org/10.1016/j.jacc.2008.10.031] [PMID: 19095139]
[73]
Davis, H.R., Jr; Compton, D.S.; Hoos, L.; Tetzloff, G. Ezetimibe, a potent cholesterol absorption inhibitor, inhibits the development of atherosclerosis in ApoE knockout mice. Arterioscler. Thromb. Vasc. Biol., 2001, 21(12), 2032-2038.
[http://dx.doi.org/10.1161/hq1201.100260] [PMID: 11742881]
[74]
Pinkosky, S.L.; Newton, R.S.; Day, E.A.; Ford, R.J.; Lhotak, S.; Austin, R.C.; Birch, C.M.; Smith, B.K.; Filippov, S.; Groot, P.H.E.; Steinberg, G.R.; Lalwani, N.D. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat. Commun., 2016, 7, 13457.
[http://dx.doi.org/10.1038/ncomms13457] [PMID: 27892461]
[75]
Burke, A.C.; Huff, M.W. ATP-citrate lyase: Genetics, molecular biology and therapeutic target for dyslipidemia. Curr. Opin. Lipidol., 2017, 28(2), 193-200.
[http://dx.doi.org/10.1097/MOL.0000000000000390] [PMID: 28059952]
[76]
Aggerbeck, L.P.; Bouma, M.E.; Eisenberg, C.; Munck, A.; Hermier, M.; Schmitz, J.; Gay, G.; Rader, D.J.; Gregg, R.E. Absence of microsomal triglyceride transfer protein in individuals with A-beta lipoproteinemia. Science, 1992, 258, 999-1001.
[http://dx.doi.org/10.1126/science.1439810]
[77]
Samaha, F.F.; McKenney, J.; Bloedon, L.T.; Sasiela, W.J.; Rader, D.J. Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia. Nat. Clin. Pract. Cardiovasc. Med., 2008, 5(8), 497-505.
[http://dx.doi.org/10.1038/ncpcardio1250] [PMID: 18506154]
[78]
Shiomi, M.; Ito, T. MTP inhibitor decreases plasma cholesterol levels in LDL receptor-deficient WHHL rabbits by lowering the VLDL secretion. Eur. J. Pharmacol., 2001, 431(1), 127-131.
[http://dx.doi.org/10.1016/S0014-2999(01)01419-4] [PMID: 11716851]
[79]
Rizzo, M. Lomitapide, a microsomal triglyceride transfer protein inhibitor for the treatment of hypercholesterolemia. IDrugs, 2010, 13(2), 103-111.
[PMID: 20127562]
[80]
Meyers, C.D.; Kamanna, V.S.; Kashyap, M.L. Niacin therapy in atherosclerosis. Curr. Opin. Lipidol., 2004, 15(6), 659-665.
[http://dx.doi.org/10.1097/00041433-200412000-00006] [PMID: 15529025]
[81]
Taylor, A.J.; Sullenberger, L.E.; Lee, H.J.; Lee, J.K.; Grace, K.A. Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation, 2004, 110(23), 3512-3517.
[http://dx.doi.org/10.1161/01.CIR.0000148955.19792.8D] [PMID: 15537681]
[82]
Kashyap, M.L.; McGovern, M.E.; Berra, K.; Guyton, J.R.; Kwiterovich, P.O.; Harper, W.L.; Toth, P.D.; Favrot, L.K.; Kerzner, B.; Nash, S.D.; Bays, H.E.; Simmons, P.D. Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia. Am. J. Cardiol., 2002, 89(6), 672-678.
[http://dx.doi.org/10.1016/S0002-9149(01)02338-4] [PMID: 11897208]
[83]
Mulvihill, E.E.; Assini, J.M.; Sutherland, B.G.; DiMattia, A.S.; Khami, M.; Koppes, J.B.; Sawyez, C.G.; Whitman, S.C.; Huff, M.W. Naringenin decreases progression of atherosclerosis by improving dyslipidemia in high-fat-fed low-density lipoprotein receptor-null mice. Arterioscler. Thromb. Vasc. Biol., 2010, 30(4), 742-748.
[http://dx.doi.org/10.1161/ATVBAHA.109.201095] [PMID: 20110573]
[84]
Orhan, I.E.; Nabavi, S.F.; Daglia, M.; Tenore, G.C.; Mansouri, K.; Nabavi, S.M. Naringenin and atherosclerosis: A review of literature. Curr. Pharm. Biotechnol., 2015, 16(3), 245-251.
[http://dx.doi.org/10.2174/1389201015666141202110216] [PMID: 25483717]
[85]
Libby, P.; Ridker, P.M.; Maseri, A. Inflammation and atherosclerosis. Circulation, 2002, 105(9), 1135-1143.
[http://dx.doi.org/10.1161/hc0902.104353] [PMID: 11877368]
[86]
Libby, P.; Ridker, P.M.; Hansson, G.K. Leducq Transatlantic Network on Atherothrombosis. Inflammation in atherosclerosis: from pathophysiology to practice. J. Am. Coll. Cardiol., 2009, 54(23), 2129-2138.
[http://dx.doi.org/10.1016/j.jacc.2009.09.009] [PMID: 19942084]
[87]
Jasińska, M.; Owczarek, J.; Orszulak-Michalak, D. Statins: A new insight into their mechanisms of action and consequent pleiotropic effects. Pharmacol. Rep., 2007, 59(5), 483-499.
[PMID: 18048949]
[88]
Bhatt, D.L.; Topol, E.J. Need to test the arterial inflammation hypothesis. Circulation, 2002, 106(1), 136-140.
[http://dx.doi.org/10.1161/01.CIR.0000021112.29409.A2] [PMID: 12093783]
[89]
Sniderman, A.; Shapiro, S.; Marpole, D.; Skinner, B.; Teng, B.; Kwiterovich, P.O., Jr Association of coronary atherosclerosis with hyperapobetalipoproteinemia. [increased protein but normal cholesterol levels in human plasma low density (beta) lipoproteins]. Proc. Natl. Acad. Sci. USA, 1980, 77(1), 604-608.
[http://dx.doi.org/10.1073/pnas.77.1.604] [PMID: 6928647]
[90]
Ishizaka, N.; Ishizaka, Y.; Toda, E.; Hashimoto, H.; Nagai, R.; Yamakado, M. Association between cigarette smoking, metabolic syndrome, and carotid arteriosclerosis in Japanese individuals. Atherosclerosis, 2005, 181(2), 381-388.
[http://dx.doi.org/10.1016/j.atherosclerosis.2005.01.026] [PMID: 16039294]
[91]
Packard, R.R.; Libby, P. Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin. Chem., 2008, 54(1), 24-38.
[http://dx.doi.org/10.1373/clinchem.2007.097360] [PMID: 18160725]
[92]
Gulcan, H.O.; Kupeli, E.; Unlu, S.; Yesilada, E.; Sahin, M.F. 4-(5-chloro-2(3H)-benzoxazolon-3-yl) butanoic acid derivatives: Synthesis, antinociceptive and anti-inflammatory properties. Arch. Pharm. (Weinheim), 2003, 336(10), 477-482.
[http://dx.doi.org/10.1002/ardp.200300722] [PMID: 14582124]
[93]
Gulcan, H.O.; Unlu, S.; Banoglu, E.; Sahin, M.F.; Kupeli, E.; Yesilada, E. Synthesis of new 4-(5-chloro-2-oxo-3H-benzoxazol-3-yl) butanamide derivatives and their analgesic and anti-Inflammatory properties. Turk. J. Chem., 2003, 27, 467-476.
[94]
FitzGerald, G.A.; Patrono, C. The coxibs, selective inhibitors of cyclooxygenase-2. N. Engl. J. Med., 2001, 345(6), 433-442.
[http://dx.doi.org/10.1056/NEJM200108093450607] [PMID: 11496855]
[95]
Dogné, J.M.; Hanson, J.; Supuran, C.; Pratico, D. Coxibs and cardiovascular side-effects: From light to shadow. Curr. Pharm. Des., 2006, 12(8), 971-975.
[http://dx.doi.org/10.2174/138161206776055949] [PMID: 16533164]
[96]
Ghosh, R.; Alajbegovic, A.; Gomes, A.V. NSAIDs and cardiovascular diseases: Role of reactive oxygen species; Oxid Med Cell Long, 2015.
[97]
Grossman, E.; Messerli, F.H. Drug-induced hypertension: an unappreciated cause of secondary hypertension. Am. J. Med., 2012, 125(1), 14-22.
[http://dx.doi.org/10.1016/j.amjmed.2011.05.024] [PMID: 22195528]
[98]
Kohli, P.; Steg, P.G.; Cannon, C.P.; Smith, S.C., Jr; Eagle, K.A.; Ohman, E.M.; Alberts, M.J.; Hoffman, E.; Guo, J.; Simon, T.; Sorbets, E.; Goto, S.; Bhatt, D.L. REACH Registry Investigators. NSAID use and association with cardiovascular outcomes in outpatients with stable atherothrombotic disease. Am. J. Med., 2014, 127(1), 53-60.e1.
[http://dx.doi.org/10.1016/j.amjmed.2013.08.017] [PMID: 24280110]
[99]
Renda, G.; Tacconelli, S.; Capone, M.L.; Sacchetta, D.; Santarelli, F.; Sciulli, M.G.; Zimarino, M.; Grana, M.; D’Amelio, E.; Zurro, M.; Price, T.S.; Patrono, C.; De Caterina, R.; Patrignani, P. Celecoxib, ibuprofen, and the antiplatelet effect of aspirin in patients with osteoarthritis and ischemic heart disease. Clin. Pharmacol. Ther., 2006, 80(3), 264-274.
[http://dx.doi.org/10.1016/j.clpt.2006.05.004] [PMID: 16952493]
[100]
Salvayre, R.; Negre-Salvayre, A.; Camaré, C. Oxidative theory of atherosclerosis and antioxidants. Biochimie, 2016, 125, 281-296.
[http://dx.doi.org/10.1016/j.biochi.2015.12.014] [PMID: 26717905]
[101]
Steinberg, D. Antioxidants and atherosclerosis. A current assessment. Circulation, 1991, 84(3), 1420-1425.
[http://dx.doi.org/10.1161/01.CIR.84.3.1420] [PMID: 1884464]
[102]
Heinecke, J.W. Oxidants and antioxidants in the pathogenesis of atherosclerosis: Implications for the oxidized low density lipoprotein hypothesis. Atherosclerosis, 1998, 141(1), 1-15.
[http://dx.doi.org/10.1016/S0021-9150(98)00173-7] [PMID: 9863534]
[103]
Meagher, E.; Rader, D.J. Antioxidant therapy and atherosclerosis: Animal and human studies. Trends Cardiovasc. Med., 2001, 11(3-4), 162-165.
[http://dx.doi.org/10.1016/S1050-1738(01)00105-0] [PMID: 11686007]
[104]
Matés, J.M.; Pérez-Gómez, C.; Núñez de Castro, I. Antioxidant enzymes and human diseases. Clin. Biochem., 1999, 32(8), 595-603.
[http://dx.doi.org/10.1016/S0009-9120(99)00075-2] [PMID: 10638941]
[105]
Esterbauer, H.; Gebicki, J.; Puhl, H.; Jürgens, G. The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radic. Biol. Med., 1992, 13(4), 341-390.
[http://dx.doi.org/10.1016/0891-5849(92)90181-F] [PMID: 1398217]
[106]
Salonen, R.M.; Nyyssönen, K.; Kaikkonen, J.; Porkkala-Sarataho, E.; Voutilainen, S.; Rissanen, T.H.; Tuomainen, T.P.; Valkonen, V.P.; Ristonmaa, U.; Lakka, H.M.; Vanharanta, M.; Salonen, J.T.; Poulsen, H.E. Antioxidant Supplementation in Atherosclerosis Prevention Study. Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study. Circulation, 2003, 107(7), 947-953.
[http://dx.doi.org/10.1161/01.CIR.0000050626.25057.51] [PMID: 12600905]
[107]
Meyers, D.G.; Maloley, P.A. The antioxidant vitamins: Impact on atherosclerosis. Pharmacotherapy, 1993, 13(6), 574-582.
[PMID: 8302680]
[108]
Bielli, A.; Scioli, M.G.; Mazzaglia, D.; Doldo, E.; Orlandi, A. Antioxidants and vascular health. Life Sci., 2015, 143, 209-216.
[http://dx.doi.org/10.1016/j.lfs.2015.11.012] [PMID: 26585821]
[109]
Pietta, P.G. Flavonoids as antioxidants. J. Nat. Prod., 2000, 63(7), 1035-1042.
[http://dx.doi.org/10.1021/np9904509] [PMID: 10924197]
[110]
Apak, R.; Güçlü, K.; Ozyürek, M.; Karademir, S.E. Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. J. Agric. Food Chem., 2004, 52(26), 7970-7981.
[http://dx.doi.org/10.1021/jf048741x] [PMID: 15612784]
[111]
Sahebkar, A. Dual effect of curcumin in preventing atherosclerosis: the potential role of pro-oxidant-antioxidant mechanisms. Nat. Prod. Res., 2015, 29(6), 491-492.
[http://dx.doi.org/10.1080/14786419.2014.956212] [PMID: 25190358]
[112]
Shin, S.K.; Ha, T.Y.; McGregor, R.A.; Choi, M.S. Long-term curcumin administration protects against atherosclerosis via hepatic regulation of lipoprotein cholesterol metabolism. Mol. Nutr. Food Res., 2011, 55(12), 1829-1840.
[http://dx.doi.org/10.1002/mnfr.201100440] [PMID: 22058071]
[113]
Bruikman, C.S.; Stoekenbroek, R.M.; Hovingh, G.K.; Kastelein, J.P. New drugs for atherosclerosis. Can. J. Cardiol., 2017, 33(3), 350-357.
[http://dx.doi.org/10.1016/j.cjca.2016.09.010] [PMID: 27993452]
[114]
Bertrand, M.J.; Tardif, J.C. Inflammation and beyond: New directions and emerging drugs for treating atherosclerosis. Expert Opin. Emerg. Drugs, 2017, 22(1), 1-26.
[http://dx.doi.org/10.1080/14728214.2017.1269743] [PMID: 27927063]
[115]
Wang, X.; Chen, X.; Zhang, X.; Su, C.; Yang, M.; He, W.; Du, Y.; Si, S.; Wang, L.; Hong, B. A small-molecule inhibitor of PCSK9 transcription ameliorates atherosclerosis through the modulation of FoxO1/3 and HNF1α. EBioMedicine, 2020, 52, 102650.
[http://dx.doi.org/10.1016/j.ebiom.2020.102650] [PMID: 32058941]
[116]
Disney, M.D. Inhibiting translation one protein at a time. Trends Biochem. Sci., 2017, 42(6), 412-413.
[http://dx.doi.org/10.1016/j.tibs.2017.04.008] [PMID: 28522328]
[117]
Srivastava, R.A.K.; Cornicelli, J.A.; Markham, B.; Bisgaier, C.L. Gemcabene, a first-in-class lipid-lowering agent in late-stage development, down-regulates acute-phase C-reactive protein via C/EBP-δ-mediated transcriptional mechanism. Mol. Cell. Biochem., 2018, 449(1-2), 167-183.
[http://dx.doi.org/10.1007/s11010-018-3353-5] [PMID: 29644527]
[118]
Stein, E.; Bays, H.; Koren, M.; Bakker-Arkema, R.; Bisgaier, C. Efficacy and safety of gemcabene as add-on to stable statin therapy in hypercholesterolemic patients. J. Clin. Lipidol., 2016, 10(5), 1212-1222.
[http://dx.doi.org/10.1016/j.jacl.2016.08.002] [PMID: 27678439]
[119]
Walsh, M.T.; Hussain, M.M. Targeting microsomal triglyceride transfer protein and lipoprotein assembly to treat homozygous familial hypercholesterolemia. Crit. Rev. Clin. Lab. Sci., 2017, 54(1), 26-48.
[http://dx.doi.org/10.1080/10408363.2016.1221883] [PMID: 27690713]
[120]
Stefanutti, C. Lomitapide–a microsomal triglyceride transfer protein inhibitor for homozygous familial hypercholesterolemia. Curr. Atheroscler. Rep., 2020, 22(8), 1-11.
[121]
Ueshima, K.; Akihisa-Umeno, H.; Nagayoshi, A.; Takakura, S.; Matsuo, M.; Mutoh, S. Implitapide, a microsomal triglyceride transfer protein inhibitor, reduces progression of atherosclerosis in apolipoprotein E knockout mice fed a Western-type diet: Involvement of the inhibition of postprandial triglyceride elevation. Biol. Pharm. Bull., 2005, 28(2), 247-252.
[http://dx.doi.org/10.1248/bpb.28.247] [PMID: 15684478]
[122]
Ray, K.K.; Bays, H.E.; Catapano, A.L.; Lalwani, N.D.; Bloedon, L.T.; Sterling, L.R.; Robinson, P.L.; Ballantyne, C.M. CLEAR Harmony Trial. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N. Engl. J. Med., 2019, 380(11), 1022-1032.
[http://dx.doi.org/10.1056/NEJMoa1803917] [PMID: 30865796]
[123]
Zhang, J.; Niimi, M.; Yang, D.; Liang, J.; Xu, J.; Kimura, T.; Mathew, A.V.; Guo, Y.; Fan, Y.; Zhu, T.; Song, J.; Ackermann, R.; Koike, Y.; Schwendeman, A.; Lai, L.; Pennathur, S.; Garcia-Barrio, M.; Fan, J.; Chen, Y.E. Deficiency of cholesteryl ester transfer protein protects against atherosclerosis in rabbits. Arterioscler. Thromb. Vasc. Biol., 2017, 37(6), 1068-1075.
[http://dx.doi.org/10.1161/ATVBAHA.117.309114] [PMID: 28428219]
[124]
Williams, S.A.; Murthy, A.C.; DeLisle, R.K.; Hyde, C.; Malarstig, A.; Ostroff, R.; Weiss, S.J.; Segal, M.R.; Ganz, P. Improving assessment of drug safety through proteomics: early detection and mechanistic characterization of the unforeseen harmful effects of torcetrapib. Circulation, 2018, 137(10), 999-1010.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.028213] [PMID: 28974520]
[125]
Vingerling, J.R.; Dielemans, I.; Bots, M.L.; Hofman, A.; Grobbee, D.E.; de Jong, P.T. Age-related macular degeneration is associated with atherosclerosis. The rotterdam study. Am. J. Epidemiol., 1995, 142(4), 404-409.
[http://dx.doi.org/10.1093/oxfordjournals.aje.a117648] [PMID: 7625405]
[126]
Di Angelantonio, E.; Sarwar, N.; Perry, P.; Kaptoge, S.; Ray, K.K.; Thompson, A.; Wood, A.M.; Lewington, S.; Sattar, N.; Packard, C.J.; Collins, R.; Thompson, S.G.; Danesh, J. Emerging risk factors collaboration. Major lipids, apolipoproteins, and risk of vascular disease. JAMA, 2009, 302(18), 1993-2000.
[http://dx.doi.org/10.1001/jama.2009.1619] [PMID: 19903920]
[127]
Plump, A.S.; Smith, J.D.; Hayek, T.; Aalto-Setälä, K.; Walsh, A.; Verstuyft, J.G.; Rubin, E.M.; Breslow, J.L. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell, 1992, 71(2), 343-353.
[http://dx.doi.org/10.1016/0092-8674(92)90362-G] [PMID: 1423598]
[128]
Hansson, G.K.; Hermansson, A. The immune system in atherosclerosis. Nat. Immunol., 2011, 12(3), 204-212.
[http://dx.doi.org/10.1038/ni.2001] [PMID: 21321594]
[129]
Tsubakio-Yamamoto, K.; Matsuura, F.; Koseki, M.; Oku, H.; Sandoval, J.C.; Inagaki, M.; Nakatani, K.; Nakaoka, H.; Kawase, R.; Yuasa-Kawase, M.; Masuda, D.; Ohama, T.; Maeda, N.; Nakagawa-Toyama, Y.; Ishigami, M.; Nishida, M.; Kihara, S.; Shimomura, I.; Yamashita, S. Adiponectin prevents atherosclerosis by increasing cholesterol efflux from macrophages. Biochem. Biophys. Res. Commun., 2008, 375(3), 390-394.
[http://dx.doi.org/10.1016/j.bbrc.2008.08.009] [PMID: 18703020]