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人C反应蛋白不会在转基因兔中促进动脉粥样硬化。

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

作者信息

Koike Tomonari, Kitajima Shuji, Yu Ying, Nishijima Kazutoshi, Zhang Jifeng, Ozaki Yukio, Morimoto Masatoshi, Watanabe Teruo, Bhakdi Sucharit, Asada Yujiro, Chen Y Eugene, Fan Jianglin

机构信息

Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-City, Yamanashi, 409-3898, Japan.

出版信息

Circulation. 2009 Nov 24;120(21):2088-94. doi: 10.1161/CIRCULATIONAHA.109.872796. Epub 2009 Nov 9.

DOI:10.1161/CIRCULATIONAHA.109.872796
PMID:19901190
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2910368/
Abstract

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.

摘要

背景

尽管基线血浆C反应蛋白（CRP）水平适度升高与未来心血管事件之间存在统计学上的显著关联，但关于CRP在动脉粥样硬化发病机制中是否起因果作用的争论仍未解决。

方法与结果

我们培育了2株表达人CRP（hCRP）的转基因（Tg）兔品系。hCRP-Tg-1和hCRP-Tg-2兔血浆中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兔血浆中分离出的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，我们将hCRP-Tg兔与非Tg兔对富含胆固醇饮食诱导的主动脉和冠状动脉粥样硬化的易感性进行了比较。在给予富含胆固醇的饮食16周后，Tg兔和非Tg兔在主动脉和冠状动脉中均出现了相似的高胆固醇血症和病变大小。免疫组织化学染色和蛋白质印迹分析显示，病变中确实存在hCRP，但hCRP并不影响病变中巨噬细胞的聚集和平滑肌细胞的增殖。

结论

hCRP-Tg兔血浆中高浓度或低浓度的hCRP均不影响主动脉或冠状动脉粥样硬化病变的形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609e/2910368/690bb2a16243/nihms221516f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609e/2910368/a1b9c39fac55/nihms221516f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609e/2910368/690bb2a16243/nihms221516f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609e/2910368/4b50694457c9/nihms221516f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609e/2910368/c5ebde268255/nihms221516f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609e/2910368/b7861e5c1595/nihms221516f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609e/2910368/2aca6fd166d1/nihms221516f4a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609e/2910368/662540dce137/nihms221516f5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609e/2910368/690bb2a16243/nihms221516f7.jpg

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