Lipoprotein(a) Cellular Uptake Ex Vivo and Hepatic Capture In Vivo Is Insensitive of PCSK9 Inhibition With Alirocumab

被引：23

作者：

Chemello, Kevin ^{[1
]}

Beeske, Sandra ^{[2
]}

Thi Thu Trang Tran ^{[2
]}

Blanchard, Valentin ^{[1
]}

Villard, Elise F. ^{[2
]}

Poirier, Bruno ^{[2
]}

Le Bail, Jean-Christophe ^{[2
]}

Dargazanli, Gihad ^{[2
]}

Ho-Van-Guimbal, Sophie ^{[2
]}

Boulay, Denis ^{[2
]}

Bergis, Olivier ^{[2
]}

Pruniaux, Marie-Pierre ^{[2
]}

Croyal, Mikael ^{[3
]}

Janiak, Philip ^{[2
]}

Guillot, Etienne ^{[2
]}

Lambert, Gilles ^{[1
]}

机构：

[1] Univ La Reunion, Lab Inserm UMR 1188 DeTROI, St Clotilde, France

[2] Sanofi R&D, Chilly Mazarin, France

[3] Univ Nantes, CRNH Ouest, Inra UMR 1280 PhAN, Nantes, France

来源：

JACC-BASIC TO TRANSLATIONAL SCIENCE | 2020年 / 5卷 / 06期

关键词：

lipoprotein(a); liver-humanized mice; low-density lipoprotein receptor; proprotein convertase subtilisin/kexin type 9; HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; RECEPTOR; CATABOLISM; EXPRESSION; LP(A); RISK;

D O I：

10.1016/j.jacbts.2020.03.008

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Lipoprotein(a) (Lp[a]) is the most common genetically inherited risk factor for cardiovascular disease. Many aspects of Lp(a) metabolism remain unknown. We assessed the uptake of fluorescent Lp(a) in primary human lymphocytes as well as Lp(a) hepatic capture in a mouse model in which endogenous hepatocytes have been ablated and replaced with human ones. Modulation of LDLR expression with the PCSK9 inhibitor alirocumab did not alter the cellular or the hepatic uptake of Lp(a), demonstrating that the LDL receptor is not a major route for Lp(a) plasma clearance. These results have clinical implications because they underpin why statins are not efficient at reducing Lp(a). (C) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

引用

页码：549 / 557

页数：9

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