Human C-Reactive Protein Does Not Promote Atherosclerosis in Transgenic Rabbits

被引：93

作者：

Koike, Tomonari ^{[1
]}

Kitajima, Shuji ^{[3
]}

Yu, Ying ^{[1
]}

Nishijima, Kazutoshi ^{[3
]}

Zhang, Jifeng ^{[1
,4
]}

Ozaki, Yukio ^{[2
]}

Morimoto, Masatoshi ^{[5
]}

Watanabe, Teruo ^{[6
]}

Bhakdi, Sucharit ^{[7
]}

Asada, Yujiro ^{[8
]}

Chen, Y. Eugene ^{[4
]}

Fan, Jianglin ^{[1
]}

机构：

[1] Univ Yamanashi, Interdisciplinary Grad Sch Med & Engn, Dept Mol Pathol, Chuo City, Yamanashi 4093898, Japan

[2] Univ Yamanashi, Interdisciplinary Grad Sch Med & Engn, Dept Clin Lab & Med, Chuo City, Yamanashi 4093898, Japan

[3] Saga Univ, Analyt Res Ctr Expt Sci, Saga 840, Japan

[4] Univ Michigan, Dept Internal Med, Ctr Cardiovasc, Ann Arbor, MI 48109 USA

[5] Kumamoto Hlth Sci Univ, Dept Rehabil, Kumamoto, Japan

[6] Fukuoka Wajiro Hosp, Fukuoka, Japan

[7] Inst Med Microbiol & Hyg, Mainz, Germany

[8] Miyazaki Univ, Fac Med, Dept Pathol 1, Miyazaki, Japan

来源：

CIRCULATION | 2009年 / 120卷 / 21期

基金：

美国国家卫生研究院;

关键词：

atherosclerosis; cardiovascular disease; coronary disease; pathology; risk factors; CORONARY-HEART-DISEASE; LOW-DENSITY-LIPOPROTEIN; E-DEFICIENT MICE; APOLIPOPROTEIN-E; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; EVENTS; CRP; ATHEROTHROMBOSIS; PREDICTION;

D O I：

10.1161/CIRCULATIONAHA.109.872796

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background-Although there is a statistically significant association between modestly raised baseline plasma C-reactive protein (CRP) values and future cardiovascular events, the debate is still unsettled in regard to whether CRP plays a causal role in the pathogenesis of atherosclerosis. Methods and Results-We generated 2 lines of transgenic (Tg) rabbits expressing human CRP (hCRP). The plasma levels of hCRP in hCRP-Tg-1 and hCRP-Tg-2 rabbits were 0.4 +/- 0.13 (n=14) and 57.8 +/- 20.6 mg/L (n=12), respectively. In addition, hCRP isolated from Tg rabbit plasma exhibited the ability to activate the rabbit complement. To define the role of hCRP in atherosclerosis, we compared the susceptibility of hCRP-Tg rabbits to cholesterol-rich diet-induced aortic and coronary atherosclerosis with that of non-Tg rabbits. After being fed with a cholesterol-rich diet for 16 weeks, Tg and non-Tg rabbits developed similar hypercholesterolemia and lesion sizes in both aortic and coronary arteries. Immunohistochemical staining and Western blotting revealed that hCRP was indeed present in the lesions but did not affect macrophage accumulation and smooth muscle cell proliferation of the lesions. Conclusions-Neither high nor low plasma concentrations of hCRP affected aortic or coronary atherosclerosis lesion formation in hCRP-Tg rabbits. (Circulation. 2009;120:2088-2094.)

引用

页码：2088 / U53

页数：14

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