Human C-reactive protein does not promote atherosclerosis in transgenic rabbits.
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.


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.
Koike
Tomonari
T
Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-City, Yamanashi, 409-3898, Japan.
Kitajima
Shuji
S
Yu
Ying
Y
Nishijima
Kazutoshi
K
Zhang
Jifeng
J
Ozaki
Yukio
Y
Morimoto
Masatoshi
M
Watanabe
Teruo
T
Bhakdi
Sucharit
S
Asada
Yujiro
Y
Chen
Y Eugene
YE
Fan
Jianglin
J
D000818:Animals; D030801:Animals, Genetically Modified; D050197:Atherosclerosis / Q000175:diagnosis / Q000209:etiology*; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis / Q000502:physiology*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D006801:Humans; D008297:Male; D011817:Rabbits
D015415:Biomarkers; D002791:Cholesterol, Dietary; D002097:C-Reactive Protein