REFERENCES
1. Roth GA, Abate D, Abate KH, et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392:1736-88.
2. Gaziano TA, Bitton A, Anand S, Abrahams-Gessel S, Murphy A. Growing epidemic of coronary heart disease in low- and middle-income countries. Curr Probl Cardiol 2010;35:72-115.
3. Cunningham KS, Gotlieb AI. The role of shear stress in the pathogenesis of atherosclerosis. Lab Investig 2005;85:9-23.
4. Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol 2013;13:709-21.
5. Shankman LS, Gomez D, Cherepanova OA, et al. KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. Nat Med 2015;21:628-37.
6. Wang Y, Dubland JA, Allahverdian S, et al. Smooth muscle cells contribute the majority of foam cells in ApoE (Apolipoprotein E)-deficient mouse atherosclerosis. Arterioscler Thromb Vasc Biol 2019;39:876-87.
7. Gonzalez L, Trigatti BL. Macrophage apoptosis and necrotic core development in atherosclerosis: a rapidly advancing field with clinical relevance to imaging and therapy. Can J Cardiol 2017;33:303-12.
9. Davidson MH. Reducing residual risk for patients on statin therapy: the potential role of combination therapy. Am J Cardiol 2005;96:3K-13K. discussion 34K-35K
10. Ridker PM, Everett BM, Thuren T, et al; CANTOS Trial Group. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med 2017;377:1119-31.
11. Benjannet S, Rhainds D, Essalmani R, et al. NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol. J Biol Chem 2004;279:48865-75.
12. Sahng WP, Moon YA, Horton JD. Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver. J Biol Chem 2004;279:50630-8.
13. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713-22.
14. Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018;379:2097-107.
15. Silverman MG, Ference BA, Im K, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: A systematic review and meta-analysis. JAMA 2016;316:1289-97.
16. Leander K, Mälarstig A, Van’t Hooft FM, et al. Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) predicts future risk of cardiovascular events independently of established risk factors. Circulation 2016;133:1230-9.
17. Karagiannis AD, Liu M, Toth PP, et al. Pleiotropic anti-atherosclerotic effects of PCSK9 inhibitorsfrom molecular biology to clinical translation. Curr Atheroscler Rep 2018;20:20.
18. Tang ZH, Peng J, Ren Z, et al. New role of PCSK9 in atherosclerotic inflammation promotion involving the TLR4/NF-κB pathway. Atherosclerosis 2017;262:113-22.
19. Giunzioni I, Tavori H, Covarrubias R, et al. Local effects of human PCSK9 on the atherosclerotic lesion. J Pathol 2016;238:52-62.
20. Denis M, Marcinkiewicz J, Zaid A, et al. Gene inactivation of proprotein convertase subtilisin/kexin type 9 reduces atherosclerosis in mice. Circulation 2012;125:894-901.
21. Tavori H, Giunzioni I, Predazzi IM, et al. Human PCSK9 promotes hepatic lipogenesis and atherosclerosis development via apoE- and LDLR-mediated mechanisms. Cardiovasc Res 2016;110:268-78.
22. Ferri N, Marchianò S, Tibolla G, et al. PCSK9 knock-out mice are protected from neointimal formation in response to perivascular carotid collar placement. Atherosclerosis 2016;253:214-24.
23. Zernecke A, Winkels H, Cochain C, et al. Meta-analysis of leukocyte diversity in atherosclerotic mouse aortas. Circ Res 2020;127:402-26.
25. Gimbrone MA Jr, García-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res 2016;118:620-36.
26. Iiyama K, Hajra L, Iiyama M, et al. Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. Circ Res 1999;85:199-207.
27. Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 2007;7:678-89.
28. Hsu S, Chu JS, Chen FF, Wang A, Li S. Effects of fluid shear stress on a distinct population of vascular smooth muscle cells. Cell Mol Bioeng 2011;4:627-36.
29. Wirka RC, Wagh D, Paik DT, et al. Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis. Nat Med 2019;25:1280-9.
30. Gomez D, Owens GK. Smooth muscle cell phenotypic switching in atherosclerosis. Cardiovasc Res 2012;95:156-64.
31. Bennett MR, Sinha S, Owens GK. Vascular smooth muscle cells in atherosclerosis. Circ Res 2016;118:692-702.
32. Misra A, Feng Z, Chandran RR, et al. Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells. Nat Commun 2018;9:2073.
33. Chappell J, Harman JL, Narasimhan VM, et al. Extensive proliferation of a subset of differentiated, yet plastic, medial vascular smooth muscle cells contributes to neointimal formation in mouse injury and atherosclerosis models. Circ Res 2016;119:1313-23.
34. Jacobsen K, Lund MB, Shim J, et al. Diverse cellular architecture of atherosclerotic plaque derives from clonal expansion of a few medial SMCs. JCI Insight 2017;2:95890.
35. Allahverdian S, Chaabane C, Boukais K, Francis GA, Bochaton-Piallat ML. Smooth muscle cell fate and plasticity in atherosclerosis. Cardiovasc Res 2018;114:540-50.
36. Allahverdian S, Chehroudi AC, McManus BM, Abraham T, Francis GA. Contribution of intimal smooth muscle cells to cholesterol accumulation and macrophage-like cells in human atherosclerosis. Circulation 2014;129:1551-9.
37. Pryma CS, Ortega C, Dubland JA, Francis GA. Pathways of smooth muscle foam cell formation in atherosclerosis. Curr Opin Lipidol 2019;30:117-24.
38. Zaid A, Roubtsova A, Essalmani R, et al. Proprotein convertase subtilisin/kexin type 9 (PCSK9): hepatocyte-specific low-density lipoprotein receptor degradation and critical role in mouse liver regeneration. Hepatology 2008;48:646-54.
39. Ding Z, Liu S, Wang X, et al. Hemodynamic shear stress via ROS modulates PCSK9 expression in human vascular endothelial and smooth muscle cells and along the mouse aorta. Antioxid Redox Signal 2015;22:760-71.
40. Ferri N, Tibolla G, Pirillo A, et al. Proprotein convertase subtilisin kexin type 9 (PCSK9) secreted by cultured smooth muscle cells reduces macrophages LDLR levels. Atherosclerosis 2012;220:381-6.
41. Grune J, Meyborg H, Bezhaeva T, et al. PCSK9 regulates the chemokine receptor CCR2 on monocytes. Biochem Biophys Res Commun 2017;485:312-8.
42. Ding Z, Liu S, Wang X, et al. Cross-talk between LOX-1 and PCSK9 in vascular tissues. Cardiovasc Res 2015;107:556-67.
43. Liu S, Deng X, Zhang P, et al. Blood flow patterns regulate PCSK9 secretion via MyD88-mediated pro-inflammatory cytokines. Cardiovasc Res 2020;116:1721-32.
44. Kühnast S, van der Hoorn JW, Pieterman EJ, et al. Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin. J Lipid Res 2014;55:2103-12.
45. Hajra L, Evans AI, Chen M, Hyduk SJ, Collins T, Cybulsky MI. The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc Natl Acad Sci USA 2000;97:9052-7.
46. Mittler R, Vanderauwera S, Suzuki N, et al. ROS signaling: the new wave? Trends Plant Sci 2011;16:300-9.
47. Li H, Horke S, Förstermann U. Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis 2014;237:208-19.
48. Goncharov NV, Avdonin PV, Nadeev AD, Zharkikh IL, Jenkins RO. Reactive oxygen species in pathogenesis of atherosclerosis. Curr Pharm Des 2015;21:1134-46.
49. Xu S, Ogura S, Chen J, Little PJ, Moss J, Liu P. LOX-1 in atherosclerosis: biological functions and pharmacological modifiers. Cell Mol Life Sci 2013;70:2859-72.
50. Cominacini L, Pasini AF, Garbin U, et al. Oxidized low density lipoprotein (ox-LDL) binding to ox-LDL receptor-1 in endothelial cells induces the activation of NF-kappaB through an increased production of intracellular reactive oxygen species. J Biol Chem 2000;275:12633-8.
51. Sun H, Krauss RM, Chang JT, Teng BB. PCSK9 deficiency reduces atherosclerosis, apolipoprotein B secretion, and endothelial dysfunction. J Lipid Res 2018;59:207-23.
52. Quan Y, Xin Y, Tian G, Zhou J, Liu X. Mitochondrial ROS-modulated mtDNA: a potential target for cardiac aging. Oxid Med Cell Longev 2020;2020:9423593.
53. Ding Z, Liu S, Wang X, Khaidakov M, Dai Y, Mehta JL. Oxidant stress in mitochondrial DNA damage, autophagy and inflammation in atherosclerosis. Sci Rep 2013;3:1077.
54. Ricci C, Pastukh V, Leonard J, et al. Mitochondrial DNA damage triggers mitochondrial-superoxide generation and apoptosis. Am J Physiol Cell Physiol 2008;294:C413-22.
55. Ding Z, Liu S, Wang X, et al. Cross-Talk between PCSK9 and damaged mtDNA in vascular smooth muscle cells: role in apoptosis. Antioxid Redox Signal 2016;25:997-1008.
56. Zarubin T, Han J. Activation and signaling of the p38 MAP kinase pathway. Cell Res 2005;15:11-8.
57. Wood CD, Thornton TM, Sabio G, Davis RA, Rincon M. Nuclear localization of p38 MAPK in response to DNA damage. Int J Biol Sci 2009;5:428-37.
58. Zhang Y, Qin W, Zhang L, et al. MicroRNA-26a prevents endothelial cell apoptosis by directly targeting TRPC6 in the setting of atherosclerosis. Sci Rep 2015;5:9401.
59. Clarke MC, Figg N, Maguire JJ, et al. Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. Nat Med 2006;12:1075-80.
60. Wu CY, Tang ZH, Jiang L, Li XF, Jiang ZS, Liu LS. PCSK9 siRNA inhibits HUVEC apoptosis induced by ox-LDL via Bcl/Bax-caspase9-caspase3 pathway. Mol Cell Biochem 2012;359:347-58.
61. Li J, Liang X, Wang Y, Xu Z, Li G. Investigation of highly expressed PCSK9 in atherosclerotic plaques and ox-LDL-induced endothelial cell apoptosis. Mol Med Rep 2017;16:1817-25.
62. Kim BJ, Ryu SW, Song BJ. JNK- and p38 kinase-mediated phosphorylation of Bax leads to its activation and mitochondrial translocation and to apoptosis of human hepatoma HepG2 cells. J Biol Chem 2006;281:21256-65.
63. De Chiara G, Marcocci ME, Torcia M, et al. Bcl-2 Phosphorylation by p38 MAPK: identification of target sites and biologic consequences. J Biol Chem 2006;281:21353-61.
64. Breitschopf K, Haendeler J, Malchow P, Zeiher AM, Dimmeler S. Posttranslational modification of Bcl-2 facilitates its proteasome-dependent degradation: molecular characterization of the involved signaling pathway. Mol Cell Biol 2000;20:1886-96.
65. Mäkinen PI, Lappalainen JP, Heinonen SE, et al. Silencing of either SR-A or CD36 reduces atherosclerosis in hyperlipidaemic mice and reveals reciprocal upregulation of these receptors. Cardiovasc Res 2010;88:530-8.
66. Febbraio M, Guy E, Silverstein RL. Stem cell transplantation reveals that absence of macrophage CD36 is protective against atherosclerosis. Arterioscler Thromb Vasc Biol 2004;24:2333-8.
67. Febbraio M, Podrez EA, Smith JD, et al. Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J Clin Invest 2000;105:1049-56.
68. Podrez EA, Febbraio M, Sheibani N, et al. Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species. J Clin Invest 2000;105:1095-108.
69. Schuster S, Rubil S, Endres M, et al. Anti-PCSK9 antibodies inhibit pro-atherogenic mechanisms in APOE*3Leiden.CETP mice. Sci Rep 2019;9:11079.
70. Ding Z, Liu S, Wang X, et al. PCSK9 regulates expression of scavenger receptors and ox-LDL uptake in macrophages. Cardiovasc Res 2018;114:1145-53.
71. Adorni MP, Cipollari E, Favari E, et al. Inhibitory effect of PCSK9 on Abca1 protein expression and cholesterol efflux in macrophages. Atherosclerosis 2017;256:1-6.
72. Silverstein RL, Febbraio M. CD36, a scavenger receptor involved in immunity, metabolism, angiogenesis, and behavior. Sci Signal 2009;2:re3.
73. Demers A, Samami S, Lauzier B, et al. PCSK9 induces CD36 degradation and affects long-chain fatty acid uptake and triglyceride metabolism in adipocytes and in mouse liver. Arterioscler Thromb Vasc Biol 2015;35:2517-25.
74. Poirier S, Mayer G, Benjannet S, et al. The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2. J Biol Chem 2008;283:2363-72.
75. Badimon L, Luquero A, Crespo J, Peña E, Borrell-Pages M. PCSK9 and LRP5 in macrophage lipid internalization and inflammation. Cardiovasc Res 2020:cvaa254.
76. Ouimet M, Barrett TJ, Fisher EA. HDL and Reverse Cholesterol Transport. Circ Res 2019;124:1505-18.
77. Bernelot Moens SJ, Neele AE, Kroon J, et al. PCSK9 monoclonal antibodies reverse the pro-inflammatory profile of monocytes in familial hypercholesterolaemia. Eur Heart J 2017;38:1584-93.
78. Drechsler M, Duchene J, Soehnlein O. Chemokines control mobilization, recruitment, and fate of monocytes in atherosclerosis. Arterioscler Thromb Vasc Biol 2015;35:1050-5.
79. Ricci C, Ruscica M, Camera M, et al. PCSK9 induces a pro-inflammatory response in macrophages. Sci Rep 2018;8:2267.
80. Tang Z, Jiang L, Peng J, et al. PCSK9 siRNA suppresses the inflammatory response induced by oxLDL through inhibition of NF-κB activation in THP-1-derived macrophages. Int J Mol Med 2012;30:931-8.
81. Ding Z, Wang X, Liu S, et al. NLRP3 inflammasome via IL-1β regulates PCSK9 secretion. Theranostics 2020;10:7100-10.
82. Feingold KR, Moser AH, Shigenaga JK, Patzek SM, Grunfeld C. Inflammation stimulates the expression of PCSK9. Biochem Biophys Res Commun 2008;374:341-4.
83. Liu L, Xie M, Jiang Z, et al. Effects of pcsk9 siRNA on THP-1 derived macrophages apoptosis induced by oxLDL. Prog Biochem Biophys 2009;36:323-330.
84. Bai XQ, Peng J, Wang MM, et al. PCSK9: a potential regulator of apoE/apoER2 against inflammation in atherosclerosis? Clin Chim Acta 2018;483:192-6.
85. Kysenius K, Muggalla P, Mätlik K, Arumäe U, Huttunen HJ. PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling. Cell Mol Life Sci 2012;69:1903-16.
86. Waltmann MD, Basford JE, Konaniah ES, Weintraub NL, Hui DY. Apolipoprotein E receptor-2 deficiency enhances macrophage susceptibility to lipid accumulation and cell death to augment atherosclerotic plaque progression and necrosis. Biochim Biophys Acta 2014;1842:1395-405.
87. Saigusa R, Winkels H, Ley K. T cell subsets and functions in atherosclerosis. Nat Rev Cardiol 2020;17:387-401.
88. Gil-Pulido J, Zernecke A. Antigen-presenting dendritic cells in atherosclerosis. Eur J Pharmacol 2017;816:25-31.
89. Liu A, Frostegård J. PCSK9 plays a novel immunological role in oxidized LDL-induced dendritic cell maturation and activation of T cells from human blood and atherosclerotic plaque. J Intern Med 2018:193-210.
90. Kim YU, Kee P, Danila D, Teng BB. A critical role of PCSK9 in mediating IL-17-producing T cell responses in hyperlipidemia. Immune Netw 2019;19:e41.
91. Taleb S, Tedgui A, Mallat Z. IL-17 and Th17 cells in atherosclerosis: subtle and contextual roles. Arterioscler Thromb Vasc Biol 2015;35:258-64.
92. Huo Y, Schober A, Forlow SB, et al. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nat Med 2003;9:61-7.
94. Gurbel PA, Navarese EP, Tantry US. Exploration of PCSK9 as a cardiovascular risk factor: is there a link to the platelet? J Am Coll Cardiol 2017;70:1463-6.
95. Pastori D, Nocella C, Farcomeni A, et al; ATHERO-AF Study Group. Relationship of PCSK9 and urinary thromboxane excretion to cardiovascular events in patients with atrial fibrillation. J Am Coll Cardiol 2017;70:1455-62.
97. Navarese EP, Kolodziejczak M, Winter MP, et al. Association of PCSK9 with platelet reactivity in patients with acute coronary syndrome treated with prasugrel or ticagrelor: the PCSK9-REACT study. Int J Cardiol 2017;227:644-9.
98. Barale C, Bonomo K, Frascaroli C, et al. Platelet function and activation markers in primary hypercholesterolemia treated with anti-PCSK9 monoclonal antibody: a 12-month follow-up. Nutr Metab Cardiovasc Dis 2020;30:282-91.
99. Camera M, Rossetti L, Barbieri SS, et al. PCSK9 as a positive modulator of platelet activation. J Am Coll Cardiol 2018;71:952-4.
101. Ason B, van der Hoorn JW, Chan J, et al. PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE. J Lipid Res 2014;55:2370-9.
102. Qi Z, Hu L, Zhang J, et al. PCSK9(Proprotein Convertase Subtilisin/Kexin 9) Enhances Platelet Activation, Thrombosis, and Myocardial Infarct Expansion by Binding to Platelet CD36. Circulation 2021;143:45-61.
103. Yang M, Cooley BC, Li W, et al. Platelet CD36 promotes thrombosis by activating redox sensor ERK5 in hyperlipidemic conditions. Blood 2017;129:2917-27.
104. Magwenzi S, Woodward C, Wraith KS, et al. Oxidized LDL activates blood platelets through CD36/NOX2-mediated inhibition of the cGMP/protein kinase G signaling cascade. Blood 2015;125:2693-703.
105. Podrez EA, Byzova TV, Febbraio M, et al. Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype. Nat Med 2007;13:1086-95.
106. Kuijpers MJ, de Witt S, Nergiz-Unal R, et al. Supporting roles of platelet thrombospondin-1 and CD36 in thrombus formation on collagen. Arterioscler Thromb Vasc Biol 2014;34:1187-92.
107. Chen K, Febbraio M, Li W, Silverstein RL. A specific CD36-dependent signaling pathway is required for platelet activation by oxidized low-density lipoprotein. Circ Res 2008;102:1512-9.
108. Hackeng C, Relou I, Pladet M, Gorter G, van Rijn H, Akkerman J. Early platelet activation by low density lipoprotein via p38MAP kinase. Thromb Haemost 2017;82:1749-56.
109. Cammisotto V, Pastori D, Nocella C, et al. PCSK9 regulates Nox2-mediated platelet activation via CD36 receptor in patients with atrial fibrillation. Antioxidants (Basel) 2020;9:296.
110. van der Laan AM, Ter Horst EN, Delewi R, et al. Monocyte subset accumulation in the human heart following acute myocardial infarction and the role of the spleen as monocyte reservoir. Eur Heart J 2014;35:376-85.
111. Prabhu SD, Frangogiannis NG. The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis. Circ Res 2016;119:91-112.
112. Miñana G, Núñez J, Bayés-Genís A, et al. Role of PCSK9 in the course of ejection fraction change after ST-segment elevation myocardial infarction: a pilot study. ESC Heart Fail 2020;7:117-22.
113. Schlüter KD, Wolf A, Weber M, Schreckenberg R, Schulz R. Oxidized low-density lipoprotein (oxLDL) affects load-free cell shortening of cardiomyocytes in a proprotein convertase subtilisin/kexin 9 (PCSK9)-dependent way. Basic Res Cardiol 2017;112:63.
114. Yang CL, Zeng YD, Hu ZX, Liang H. PCSK9 promotes the secretion of pro-inflammatory cytokines by macrophages to aggravate H/R-induced cardiomyocyte injury via activating NF-κB signalling. Gen Physiol Biophys 2020;39:123-34.
115. Ding Z, Wang X, Liu S, et al. PCSK9 expression in the ischaemic heart and its relationship to infarct size, cardiac function, and development of autophagy. Cardiovasc Res 2018;114:1738-51.
116. Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011;13:132-41.
117. Gui D, Cui Z, Zhang L, et al. Salidroside attenuates hypoxia-induced pulmonary arterial smooth muscle cell proliferation and apoptosis resistance by upregulating autophagy through the AMPK-mTOR-ULK1 pathway. BMC Pulm Med 2017;17:191.
118. Matsui Y, Takagi H, Qu X, et al. Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circ Res 2007;100:914-22.
119. Angin Y, Steinbusch LK, Simons PJ, et al. CD36 inhibition prevents lipid accumulation and contractile dysfunction in rat cardiomyocytes. Biochem J 2012;448:43-53.
120. Nagendran J, Pulinilkunnil T, Kienesberger PC, et al. Cardiomyocyte-specific ablation of CD36 improves post-ischemic functional recovery. J Mol Cell Cardiol 2013;63:180-8.
121. Zhang Y, Bao M, Dai M, et al. Cardiospecific CD36 suppression by lentivirus-mediated RNA interference prevents cardiac hypertrophy and systolic dysfunction in high-fat-diet induced obese mice. Cardiovasc Diabetol 2015;14:69.
122. Sung MM, Byrne NJ, Kim TT, et al. Cardiomyocyte-specific ablation of CD36 accelerates the progression from compensated cardiac hypertrophy to heart failure. Am J Physiol Heart Circ Physiol 2017;312:H552-60.
123. Abifadel M, Varret M, Rabès JP, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003;34:154-6.
124. Robinson JG, Farnier M, Krempf M, et al; ODYSSEY LONG TERM Investigators. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1489-99.
