Experimental Animal Models Evaluating the Causal Role of Lipoprotein(a) in Atherosclerosis and Aortic Stenosis

Cardiovascular Drugs and Therapy
Calvin YeangSotirios Tsimikas

Abstract

Lipoprotein(a) [Lp(a)], comprised of apolipoprotein(a) [apo(a)] and a low-density lipoprotein-like particle, is a genetically determined, causal risk factor for cardiovascular disease and calcific aortic valve stenosis. Lp(a) is the major plasma lipoprotein carrier of oxidized phospholipids, is pro-inflammatory, inhibits plasminogen activation, and promotes smooth muscle cell proliferation, as defined mostly through in vitro studies. Although Lp(a) is not expressed in commonly studied laboratory animals, mouse and rabbit models transgenic for Lp(a) and apo(a) have been developed to address their pathogenicity in vivo. These models have provided significant insights into the pathophysiology of Lp(a), particularly in understanding the mechanisms of Lp(a) in mediating atherosclerosis. Studies in Lp(a)-transgenic mouse models have demonstrated that apo(a) is retained in atheromas and suggest that it promotes fatty streak formation. Furthermore, rabbit models have shown that Lp(a) promotes atherosclerosis and vascular calcification. However, many of these models have limitations. Mouse models need to be transgenic for both apo(a) and human apolipoprotein B-100 since apo(a) does not covalently associated with mouse apoB to form Lp(a)...Continue Reading

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Citations

Jun 5, 2016·Progress in Biophysics and Molecular Biology·Christine BaumgartnerMartin Ungerer
Dec 27, 2016·Journal of Cellular Biochemistry·Hyunju ChoiCheorl-Ho Kim
Nov 3, 2016·Journal of Lipid Research·Børge G Nordestgaard, Anne Langsted
Apr 30, 2017·European Heart Journal·Arnold von Eckardstein
Dec 27, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Yunosuke MatsuuraKarin E Bornfeldt
Jul 26, 2019·Journal of Clinical Medicine·Willemien van ZwolJan Albert Kuivenhoven
Sep 20, 2018·Hormones : International Journal of Endocrinology and Metabolism·Niki Katsiki, Dimitri P Mikhailidis
Nov 18, 2017·JACC. Basic to Translational Science·Michael TorzewskiSotirios Tsimikas
Feb 13, 2021·Cardiovascular Research·Magnus Bäck, Jean-Baptiste Michel
Apr 30, 2021·Circulation Research·Mark C BlaserElena Aikawa

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