C-reactive protein promotes vascular endothelial dysfunction partly via activating adipose tissue inflammation in hyperlipidemic rabbits
C-reactive protein promotes vascular endothelial dysfunction partly via activating adipose tissue inflammation in hyperlipidemic rabbits
复制标题
C反应蛋白部分通过激活高脂血症兔的脂肪组织炎症来促进血管内皮功能障碍。
DOI：
10.1016/j.ijcard.2013.01.158
复制
发表时间：
2013-10-03
影响因子：
3.5
通讯作者：
Wang, JingFeng
中科院分区：
文献类型：
--
作者：
Chen, YangXin;Wang, XiaoQiao;Wang, JingFeng
背景：内皮功能障碍是动脉粥样硬化形成的基础和原始标志。有证据表明，C反应蛋白（CRP）和血管周围脂肪组织（PVAT）在动脉粥样硬化中起着关键作用。方法：分别测定家兔基础总胆固醇、低密度脂蛋白胆固醇、甘油三酯、CRP、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、一氧化氮（NO）和内皮素-1（ET-1）水平，并评价内皮依赖性血管舒张功能。将动物随机分为PVAT（-）组和PVAT（+）组（去除或保留心包脂肪组织（PCAT））。两组均给予高脂饮食6周，然后给予持续CRP治疗1周，于此时间点再次测定上述各项指标。此外，分别通过聚合酶链反应和免疫印迹法评估经CRP处理的PCAT和培养的脂肪细胞中TNF-α、IL-6和巨噬细胞趋化蛋白-1（MCP-1）的mRNA和蛋白表达。高脂饮食显著增加血脂和炎症指标，诱导内皮功能障碍和NO与ET-1失衡，增加TNF-α mRNA和蛋白表达，IL-6、MCP-1和增强的PCAT巨噬细胞浸润。CRP可进一步促进巨噬细胞对PVAT的浸润，诱导NO和ET-1失衡，加重PVAT（+）动脉的内皮功能障碍，并可增强PCAT和脂肪细胞上述mRNA和蛋白的表达。CRP可明显促进高脂饮食兔血管内皮功能障碍，尤以PVAT（+）组为甚，这可能部分通过激活脂肪组织的炎症反应来介导。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Background: Endothelial dysfunction is the basic and original sign of atherogenesis. Some evidences show that C-reactive protein (CRP) and perivascular adipose tissue (PVAT) play a pivotal role in atherosclerosis. However, the effects of CRP on atherosclerosis and the related mechanisms require elucidation.Methods: The levels of basic total cholesterol, low-density lipoprotein cholesterol, triglyceride, CRP, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), nitric oxide (NO) and endothelin-1 (ET-1) were respectively measured in rabbits, endothelium-dependent vasorelaxation function was also evaluated. Animals were randomly divided into two groups: PVAT(-) and PVAT(+) group (removing or keeping pericarotid adipose tissue (PCAT)). Both of the two groups were exposed to a high-fat diet for six-week, and then sustained CRP treatment was performed for a week, at this time point all the above parameters were remeasured. In addition, mRNA and protein expression of TNF-alpha, IL-6, and macrophage chemoattractant protein-1 (MCP-1) were respectively evaluated by Polymerase Chain Reaction and immunoblotting in PCAT and cultured adipocytes treated by CRP.Results: High-fat diet greatly increased the serum lipids and inflammatory markers, induced endothelial dysfunction and imbalance between NO and ET-1, increased mRNA and protein expression of TNF-alpha, IL-6, MCP-1 and enhanced macrophage infiltration of PCAT. CRP treatment could further promote macrophage infiltration of PVAT, induce the imbalance between NO and ET-1, aggravate endothelial dysfunction especially in PVAT(+) arteries, and could also enhance the above-mentioned mRNA and protein expression in PCAT and cultured adipocytes.Conclusions: CRP could significantly promote endothelial dysfunction in high-fat diet rabbits especially in PVAT(+) groups, which may be partly mediated by activating inflammatory reaction of adipose tissue. (C) 2013 Elsevier Ireland Ltd. All rights reserved.