Emerging clinical role of proprotein convertase subtilisin/kexin type 9 inhibition-Part one: Pleiotropic pro-atherosclerotic effects of PCSK9

被引:2
作者
Zhang, Alexander M. Cao [1 ]
Ziogos, Efthymios [2 ]
Harb, Tarek [2 ]
Gerstenblith, Gary [2 ]
Leucker, Thorsten M. [2 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD USA
[2] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, 600 North Wolfe St,Halsted 500, Baltimore, MD 21287 USA
关键词
atherosclerosis; lipid metabolism; PCSK9; HEMODYNAMIC SHEAR-STRESS; ACUTE CORONARY SYNDROME; SMOOTH-MUSCLE-CELLS; FAMILIAL HYPERCHOLESTEROLEMIA; CARDIOVASCULAR-DISEASE; LIPOPROTEIN METABOLISM; REDUCING LIPIDS; HEART-DISEASE; PLASMA PCSK9; LOW LDL;
D O I
10.1111/eci.14273
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily recognized for its role in lipid metabolism, but recent evidence suggests that it may have broader implications due to its diverse tissue expression.ObjectiveThis review aims to explore the multifaceted functions of PCSK9, highlighting its pro-atherosclerotic effects, including its impact on circulating lipoprotein variables, non-low-density lipoprotein receptors, and various cell types involved in atherosclerotic plaque development.ConclusionsPCSK9 exhibits diverse roles beyond lipid metabolism, potentially contributing to atherosclerosis through multiple pathways. Understanding these mechanisms could offer new insights into therapeutic strategies targeting PCSK9 for cardiovascular disease management. Proprotein convertase subtilisin/kexin type 9 (PCSK9) exhibit diverse pro-atherosclerotic effects, impacting circulating lipoprotein variables, non-LDL receptors and key cell types involved in atherosclerotic plaque formation.image
引用
收藏
页数:12
相关论文
共 97 条
[1]   Mutations in PCSK9 cause autosomal dominant hypercholesterolemia [J].
Abifadel, M ;
Varret, M ;
Rabès, JP ;
Allard, D ;
Ouguerram, K ;
Devillers, M ;
Cruaud, C ;
Benjannet, S ;
Wickham, L ;
Erlich, D ;
Derré, A ;
Villéger, L ;
Farnier, M ;
Beucler, I ;
Bruckert, E ;
Chambaz, J ;
Chanu, B ;
Lecerf, JM ;
Luc, G ;
Moulin, P ;
Weissenbach, J ;
Prat, A ;
Krempf, M ;
Junien, C ;
Seidah, NG ;
Boileau, C .
NATURE GENETICS, 2003, 34 (02) :154-156
[2]   Inhibitory effect of PCSK9 on Abca1 protein expression and cholesterol efflux in macrophages [J].
Adorni, Maria Pia ;
Cipollari, Eleonora ;
Favari, Elda ;
Zanotti, Ilaria ;
Zimetti, Francesca ;
Corsini, Alberto ;
Ricci, Chiara ;
Bernini, Franco ;
Ferri, Nicola .
ATHEROSCLEROSIS, 2017, 256 :1-6
[3]  
Allard Delphine, 2005, Hum Mutat, V26, P497, DOI 10.1002/humu.9383
[4]   Lipoprotein(a) Levels in Familial Hypercholesterolemia An Important Predictor of Cardiovascular Disease Independent of the Type of LDL Receptor Mutation [J].
Alonso, Rodrigo .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2014, 63 (19) :1983-1989
[5]   Plasma PCSK9 Is Associated with Age, Sex, and Multiple Metabolic Markers in a Population-Based Sample of Children and Adolescents [J].
Baass, Alexis ;
Dubuc, Genevieve ;
Tremblay, Michel ;
Delvin, Edgard E. ;
O'Loughlin, Jennifer ;
Levy, Emile ;
Davignon, Jean ;
Lambert, Marie .
CLINICAL CHEMISTRY, 2009, 55 (09) :1637-1645
[6]   PCSK9 and LRP5 in macrophage lipid internalization and inflammation [J].
Badimon, Lina ;
Luquero, Aureli ;
Crespo, Javier ;
Pena, Esther ;
Borrell-Pages, Maria .
CARDIOVASCULAR RESEARCH, 2021, 117 (09) :2054-2067
[7]   PCSK9: A potential regulator of apoE/apoER2 against inflammation in atherosclerosis? [J].
Bai, Xue-qin ;
Peng, Juan ;
Wang, Mei-mei ;
Xiao, Jun ;
Xiang, Qiong ;
Ren, Zhong ;
Wen, Hong-yan ;
Jiang, Zhi-sheng ;
Tang, Zhi-han ;
Liu, Lu-shan .
CLINICA CHIMICA ACTA, 2018, 483 :192-196
[8]   Platelet function and activation markers in primary hypercholesterolemia treated with anti-PCSK9 monoclonal antibody: A 12-month follow-up [J].
Barale, Cristina ;
Bonomo, Katia ;
Frascaroli, Chiara ;
Morotti, Alessandro ;
Guerrasio, Angelo ;
Cavalot, Franco ;
Russo, Isabella .
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES, 2020, 30 (02) :282-291
[9]   The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A-Functional consequences of natural mutations and post-translational modifications [J].
Benjannet, Suzanne ;
Rhainds, David ;
Hamelin, Josee ;
Nassoury, Nasha ;
Seidah, Nabil G. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (41) :30561-30572
[10]   Atheroprotective signaling mechanisms activated by steady laminar flow in endothelial cells [J].
Berk, Bradford C. .
CIRCULATION, 2008, 117 (08) :1082-1089