C-reactive protein in atherosclerotic lesions - Its origin and pathophysiological significance
C-reactive protein in atherosclerotic lesions - Its origin and pathophysiological significance
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DOI：
10.1016/s0002-9440(10)61202-3
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发表时间：
2005-10-01
影响因子：
6
通讯作者：
Fan, JL
中科院分区：
文献类型：
--
作者：
Sun, HJ;Koike, T;Fan, JL
C-反应蛋白（CRP）常沉积在动脉内膜病变中，然而，CRP在这些病变中的起源和病理意义尚不完全清楚。在这项研究中，我们测量了高胆固醇血症家兔血浆中的CRP水平，并使用家兔和人动脉粥样硬化标本研究了CRP在mRNA和蛋白水平上的表达。CRP水平显着升高，胆固醇喂养和渡边遗传性高血脂症兔，CRP水平与主动脉粥样硬化病变的大小明显相关。免疫组化染色结合Western印迹分析显示，CRP免疫反应蛋白被发现在动脉粥样硬化的一个阶段，从早期到先进的病变。CRP存在于细胞外并与载脂蛋白B共定位，但很少与巨噬细胞和泡沫细胞的细胞质相关。实时逆转录-聚合酶链反应分析显示，CRP mRNA在动脉粥样硬化病变几乎检测不到，分离的巨噬细胞不表达CRP mRNA，这表明CRP蛋白在病变中发现的基本上是来自循环，而不是合成从头血管细胞。这些结果表明，血浆CRP和动脉粥样硬化程度之间存在联系，抑制血浆CRP可能代表治疗心血管疾病的治疗方式。
C-reactive protein (CRP) is frequently deposited in the lesions of the arterial intima; however, the origin and pathological significance of CRP in these lesions are not completely understood. in this study, we measured CRP levels in the plasma of hypercholesterolemic rabbits and investigated CRP expression at both the mRNA and protein levels using rabbit and human atherosclerotic specimens. CRP levels were significantly elevated in both cholesterol-fed and Watanabe heritable hyperlipidemic rabbits, and CRP levels were clearly correlated with aortic atherosclerotic lesion size. Immunohistochemical staining coupled with Western blotting analysis revealed that CRP-immunoreactive proteins were found at an stages of atherosclerosis from the early to advanced lesions. CRP was present extracellularly and co-localized with apolipoprotein B but was rarely associated with the cytoplasm of macrophages and foam cells. Real-time reverse transcriptase-polymerase chain reaction analysis revealed that CRP mRNA in atherosclerotic lesions was barely detectable, and isolated macrophages did not express CRP mRNA, suggesting that CRP proteins found in the lesions were essentially derived from the circulation rather than synthesized de novo by vascular cells. These results suggest that there is a link between plasma CRP and the degree of atherosclerosis and that inhibition of plasma CRP may represent a therapeutic modality for the treatment of cardiovascular disease.