内皮CXCR7缺失破坏血管稳态并损害心肌梗死后心脏重构

Loss of Endothelial CXCR7 Impairs Vascular Homeostasis and Cardiac Remodeling After Myocardial Infarction
2017-04-18 11:24发表评论
作者:Huifeng Hao, Sheng Hu, Hong Chen, Dawei Bu, Liyuan Zhu, Chuansheng Xu, Fei Chu, Xingyu Huo, Yue Tang, Xiaogang Sun, Bi-Sen Ding, De-Pei Liu, Shengshou Hu, Miao Wang
机构: 中国医学科学院中国协和医科大学
期刊: CIRCULATION2017年3月13期135卷

"BACKGROUND: Genome-wide association studies identified the association of the CXCL12 genetic locus (which encodes the chemokine CXCL12, also known as stromal cell-derived factor 1) with coronary artery disease and myocardial infarction (MI). Unlike CXCR4, the classic receptor for CXCL12, the function of CXCR7 (the most recently identified receptor) in vascular responses to injury and in MI remains unclear.

METHODS: Tissue expression of CXCR7 was examined in arteries from mice and humans. Mice that harbored floxed CXCR7 and Cdh5-promoter driven CreERT2 were treated with tamoxifen to induce endothelium-restricted deletion of CXCR7. The resulting conditional knockout mice and littermate controls were studied for arterial response to angioplasty wire injury and cardiac response to coronary artery ligation. The role of CXCR7 in endothelial cell proliferation and angiogenesis was determined in vitro with cells from mice and humans. The effects of adenoviral delivery of CXCR7 gene and pharmacological activation of CXCR7 were evaluated in mice subjected to MI.

RESULTS: Injured arteries from both humans and mice exhibited endothelial CXCR7 expression. Conditional endothelial CXCR7 deletion promoted neointimal formation without altering plasma lipid levels after endothelial injury and exacerbated heart functional impairment after MI, with increased both mortality and infarct sizes. Mechanistically, the exacerbated responses in vascular and cardiac remodeling are attributable to the key role of CXCR7 in promoting endothelial proliferation and angiogenesis. Impressively, the impaired post-MI cardiac remodeling occurred with elevated levels of CXCL12, which was previously thought to mediate cardiac protection by exclusively engaging its cognate receptor, CXCR4. In addition, both CXCR7 gene delivery via left ventricular injection and treatment with a CXCR7 agonist offered cardiac protection after MI.

CONCLUSIONS: CXCR7 represents a novel regulator of vascular homeostasis that functions in the endothelial compartment with sufficient capacity to affect cardiac function and remodeling after MI. Activation of CXCR7 may have therapeutic potential for clinical restenosis after percutaneous coronary intervention and for heart remodeling after MI."

通讯机构:From State Key Laboratory of Cardiovascular Disease (H.H., Sheng Hu, D.B., L.Z., C.X., F.C., X.H., Shengshou Hu, M.W.), Animal Experimental Center (Y.T.), Department of Cardiovascular Surgery (X.S., Shengshou Hu), and Clinical Pharmacology Center (M.W.), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Pharmacology, Shihezi University, Shihezi, Xinjiang, China (C.X.); Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui, China (F.C.); Ansary Stem Cell Institute and Department of Genetic Medicine, Weill Cornell Medicine, New York, NY (B.D.); and State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (D.L.).
学科代码:心血管病学   关键词:内皮 CXCR7缺失 血管稳态 心肌梗死 ,中国作者重要发表 爱思唯尔医学网, Elseviermed
来源: Scopus
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