Human C-reactive protein does not promote atherosclerosis in transgenic rabbits.
Human C-reactive protein does not promote atherosclerosis in transgenic rabbits.
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DOI：
10.1161/circulationaha.109.872796
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发表时间：
2009-11-24
期刊：
影响因子：
37.8
通讯作者：
Fan J
中科院分区：
文献类型：
--
作者：
Koike T;Kitajima S;Yu Y;Nishijima K;Zhang J;Ozaki Y;Morimoto M;Watanabe T;Bhakdi S;Asada Y;Chen YE;Fan J
虽然有一个统计学显着之间的关系适度提高基线血浆C反应蛋白（CRP）值和未来的心血管事件，争论仍然是悬而未决的CRP是否在动脉粥样硬化的发病机制中发挥因果作用。我们产生了两种表达人CRP（hCRP）的转基因（Tg）兔系。hCRP-Tg-1和hCRP-Tg-2家兔血浆hCRP水平分别为0.4 ± 0.13（n=14）和57.8 ± 20.6 mg/L（n=12）。此外，从Tg兔血浆中分离的hCRP表现出激活兔补体的能力。为了确定hCRP在动脉粥样硬化中的作用，我们比较了hCRP-Tg兔与非Tg兔对高胆固醇饮食诱导的主动脉和冠状动脉粥样硬化的易感性。在用富含胆固醇的饮食喂养16周后，Tg和非Tg兔在主动脉和冠状动脉中出现了相似的高胆固醇血症和病变大小。免疫组化染色和Western印迹显示hCRP确实存在于病变中，但不影响病变的巨噬细胞积聚和平滑肌细胞增殖。在hCRP-Tg兔中，高或低血浆浓度的人CRP均不影响主动脉或冠状动脉粥样硬化病变的形成。
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 as to whether CRP plays a causal role in the pathogenesis of atherosclerosis. We generated two 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. Also, 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. Neither high nor low plasma concentrations of human CRP affected aortic or coronary atherosclerosis lesion formation in hCRP-Tg rabbits.