同型半胱氨酸通过激活血管紧张素II型受体,促进成纤维细胞迁移,加重动脉粥样硬化。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Zhibo Zhu, Sujuan Li, Yuchen Jia, Jianqiang Guo
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引用次数: 0

摘要

本研究阐明了同型半胱氨酸对体外成纤维细胞(AFs)的影响及其与血管紧张素II型1受体(AT1R)的关系。高同型半胱氨酸血症加重了斑块面积,增加了斑块和主动脉外膜中IL-6、MCP-1的表达和巨噬细胞浸润,而替米沙坦改善了这一作用。高同型半胱氨酸血症诱导AFs标记蛋白ER-TR7在斑块和主动脉全层的发生,而替米沙坦改善了这些作用,表明同型半胱氨酸诱导AFs迁移,而AT1R介导了这一过程。AFs的迁移实验也得出了相同的结论。同型半胱氨酸增加了转染AT1R质粒的AFs和HEK293A细胞中PKC和ERK1/2的磷酸化水平,而替米沙坦抑制了这一作用,表明同型半胱氨酸激活了AT1R胞内信号通路。同型半胱氨酸也增加了AFs At1R的表达。结论:同型半胱氨酸通过激活AT1R,促进动脉外膜炎症,诱导心房纤颤迁移,加重动脉粥样硬化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Homocysteine promotes migration of adventitial fibroblasts via angiotensin II type 1 receptor activation to aggravate atherosclerosis.

This study clarified the effect of homocysteine on adventitial fibroblasts (AFs) and its relationship with angiotensin II type 1 receptor (AT1R). Hyperhomocysteinemia aggravated the plaque area and increased the expression of IL-6, MCP-1, and macrophage infiltration in the plaque and adventitia of the aorta, whereas telmisartan improved this effect. Hyperhomocysteinemia induced the occurrence of the AFs marker protein ER-TR7 in the plaque and entire layer of the aorta, whereas telmisartan improved these effects, indicating that homocysteine induced AFs migration and that AT1R mediated this process. The migration experiments of AFs also reached the same conclusion. Homocysteine increased the phosphorylation levels of PKC and ERK1/2 in the AFs and HEK293A cells transfected with the AT1R plasmid, whereas telmisartan inhibited this effect, indicating that homocysteine activated AT1R intracellular signaling pathway. Homocysteine also increased the AFs At1R expression. Conclusion, homocysteine promoted adventitial inflammation, induced AFs migration, and aggravated atherosclerosis by activating AT1R.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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