Human Apolipoprotein A-II Protects Against Diet-induced Atherosclerosis in Transgenic Rabbits

Overview

Journal Arterioscler Thromb Vasc Biol

Date 2012 Dec 18

PMID 23241412

Citations 38

Authors

Yao Wang

Manabu Niimi

Kazutoshi Nishijima

Ahmed Bilal Waqar

Ying Yu

Tomonari Koike

Shuji Kitajima

Enqi Liu

Tomohiro Inoue

Masayuki Kohashi

Yuka Keyamura

Tomohiro Yoshikawa

Jifeng Zhang

Loretta Ma

Xiaohui Zha

Teruo Watanabe

Yujiro Asada

Y Eugene Chen

Jianglin Fan

Affiliations

Soon will be listed here.

Abstract

Objective: Apolipoprotein (apo) A-II is the second major apo of high-density lipoproteins, yet its pathophysiological roles in the development of atherosclerosis remain unknown. We aimed to examine whether apo A-II plays any role in atherogenesis and, if so, to elucidate the mechanism involved.

Methods And Results: We compared the susceptibility of human apo A-II transgenic (Tg) rabbits to cholesterol diet-induced atherosclerosis with non-Tg littermate rabbits. Tg rabbits developed significantly less aortic and coronary atherosclerosis than their non-Tg littermates, while total plasma cholesterol levels were similar. Atherosclerotic lesions of Tg rabbits were characterized by reduced macrophages and smooth muscle cells, and apo A-II immunoreactive proteins were frequently detected in the lesions. Tg rabbits exhibited low levels of plasma C-reactive protein and blood leukocytes compared with non-Tg rabbits, and high-density lipoproteins of Tg rabbit plasma exerted stronger cholesterol efflux activity and inhibitory effects on the inflammatory cytokine expression by macrophages in vitro than high-density lipoproteins isolated from non-Tg rabbits. In addition, β-very-low-density lipoproteins of Tg rabbits were less sensitive to copper-induced oxidation than β-very-low-density lipoproteins of non-Tg rabbits.

Conclusions: These results suggest that enrichment of apo A-II in high-density lipoprotein particles has atheroprotective effects and apo A-II may become a target for the treatment of atherosclerosis.

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