Human apolipoprotein A-II protects against diet-induced atherosclerosis in transgenic rabbits.

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.

• 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
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 33 Issue 2 Pg. 224-31 (Feb 2013) ISSN: 1524-4636 [Electronic] United States
• PMID: 23241412 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• APOA2 protein, human
• Apolipoprotein A-II
• Cholesterol, Dietary
• Cytokines
• Inflammation Mediators
• Lipoproteins, HDL
• Lipoproteins, LDL
• Lipoproteins, VLDL
• oxidized low density lipoprotein

Topics

• Animals
• Animals, Genetically Modified
• Aorta (immunology, metabolism, pathology)
• Aortic Diseases (blood, etiology, genetics, immunology, pathology, prevention & control)
• Apolipoprotein A-II (blood, genetics, metabolism)
• Atherosclerosis (blood, etiology, genetics, immunology, pathology, prevention & control)
• Cholesterol, Dietary (blood)
• Coronary Artery Disease (blood, etiology, genetics, immunology, pathology, prevention & control)
• Coronary Vessels (immunology, metabolism, pathology)
• Cytokines (blood)
• Disease Models, Animal
• Female
• Humans
• Inflammation Mediators (blood)
• Lipoproteins, HDL (blood)
• Lipoproteins, LDL (blood)
• Lipoproteins, VLDL (blood)
• Male
• Oxidation-Reduction
• Plaque, Atherosclerotic
• Rabbits
• Time Factors