Activation of CXCR7 alleviates cardiac insufficiency after myocardial infarction by promoting angiogenesis and reducing apoptosis

Biomedicine & Pharmacotherapy

Li Jiang¹  Min Zhang²  Yi Xie²  Jingwen Yue²  Sheng Zhang²  Zhuowang Ge³ 

[1] Corresponding authors at: Division of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xianxia Road, Shanghai, China.;Division of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 200336, China;Division of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, China;

关键词: CXCR7;    myocardial infarction;    human umbilical endothelial cells;    angiogenesis;    apoptosis;    cardiac function;   

DOI  :  

来源: DOAJ

【 摘 要 】

Angiogenesis is an important pathway for revascularization of ischemic tissues after acute myocardial infarction (AMI). It is unclear what role CXCR7 plays in angiogenesis in the ischemic area after AMI, although some researchers have shown that the activation of CXCR7 protectsthe heart under those conditions. Here, we hypothesize that the activation of CXCR7 promotes angiogenesis, reduces cell apoptosis and alleviates cardiac deficiency after AMI. C57BL/6 J mice were subjected to AMI and treated with TC14012 (10 mg/kg) for 24 days. HUVECs were cultured in a hypoxic (2% O2) environment to generate a model of hypoxia. CXCR7 was knocked down in HUVECs by sh-CXCR7 transfection, and CXCR7 was activated by TC14012 (30 μM) treatment. The results showed that CXCR7 was downregulated in infarcted heart tissue and hypoxic HUVECs. The global activation of CXCR7 may alleviate the decrease in cardiac function indexes — (ejection fraction and fraction shortening), and reduce infarct size after AMI.. Moreover, CXCR7 activation has been shown to enhance the level of angiogenesis in ischemic heart tissue. In vitro, hypoxia-induced angiogenic functional loss and apoptosis are aggravated by CXCR7 knockdown in HUVECs. Both angiogenic impairment and cell apoptosis are rescued by CXCR7 activation. In conclusion, the present study indicates that activation of CXCR7 plays an important protective role for ischemic cells in hypoxic endothelial cells and AMI model mice by promoting angiogenesis and reducing apoptosis, which suggests that CXCR7 may be a potential therapeutic target to rescue the ischemic myocardium..

【 授权许可】

Unknown