Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 33, Issue 2, Pages 224-+Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.112.300445
Keywords
apolipoproteins; atherosclerosis; lipoproteins; metabolism; transgenic rabbits
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Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan [71790514, 19390099, 21659078, 22390068]
- National Institutes of Health [HL088391, HL068878, HL105114]
- Ministry of Health, Labor and Welfare of Japan
- AstraZeneca
- Grants-in-Aid for Scientific Research [19390099, 22390068, 25430091, 23790359, 21659078, 22500386] Funding Source: KAKEN
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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, beta-very-low-density lipoproteins of Tg rabbits were less sensitive to copper-induced oxidation than beta-very-low-density lipoproteins of non-Tg rabbits. Conclusion-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. (Arterioscler Thromb Vasc Biol. 2013; 33: 224-231.)
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