Journal
CIRCULATION
Volume 120, Issue 21, Pages 2088-U53Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.109.872796
Keywords
atherosclerosis; cardiovascular disease; coronary disease; pathology; risk factors
Funding
- Ministry of Education, Culture, Sports, Science, and Technology, Japan [19390099, 21659078]
- Ministry of Health, Labor, and Welfare of Japan
- National Institutes of Health [R01HL088391]
- American Heart Association [0835237N, 0840025N]
- Takeda Science Foundation
- ONO Medical Research Foundation
- The Naito Foundation
- The Uehara Memorial Foundation
- Japan Heart Foundation
- AstraZeneca
- Grants-in-Aid for Scientific Research [19390099, 21659078] Funding Source: KAKEN
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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.)
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