Chen YangXin, Wang XiaoQiao, Mai JingTing, Zhao XiaoMiao, Liang YongHong, Gu MiaoNing, Chen ZhongQing, Nie RuQiong, Wang JingFeng
Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, 510120, China.
Int J Cardiol. 2013 Oct 3;168(3):2397-403. doi: 10.1016/j.ijcard.2013.01.158. Epub 2013 Feb 27.
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.
The levels of basic total cholesterol, low-density lipoprotein cholesterol, triglyceride, CRP, tumor necrosis factor-α (TNF-α), 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-α, 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.
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-α, 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.
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.
内皮功能障碍是动脉粥样硬化发生的基本和初始标志。一些证据表明，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关键作用。然而，CRP对动脉粥样硬化的影响及其相关机制尚需阐明。
分别测定家兔的基础总胆固醇、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，同时评估内皮依赖性血管舒张功能。动物随机分为两组：PVAT（-）组和PVAT（+）组（去除或保留颈动脉周围脂肪组织（PCAT））。两组均给予高脂饮食6周，然后持续进行CRP治疗1周，此时重新测定上述所有参数。此外，通过聚合酶链反应和免疫印迹分别评估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。
高脂饮食显著升高血脂和炎症标志物水平，诱导内皮功能障碍以及NO与ET-1失衡，增加TNF-α、IL-6、MCP-1的mRNA和蛋白表达，并增强PCAT的巨噬细胞浸润。CRP治疗可进一步促进PVAT的巨噬细胞浸润，诱导NO与ET-1失衡，加重内皮功能障碍，尤其是在PVAT（+）动脉中，还可增强PCAT和培养的脂肪细胞中上述mRNA和蛋白表达。
CRP可显著促进高脂饮食家兔尤其是PVAT（+）组的内皮功能障碍，这可能部分是通过激活脂肪组织的炎症反应介导的。
Zotero 插件