![]() ![]() Therefore, the identification of new diagnostic and therapeutic targets in hypoxia-induced heart failure for improving the prognosis of heart failure patients is required. In turn, hypoxia exacerbates the deterioration of heart failure patients, thereby establishing a vicious circle of increasing hypoxia and subsequent malignant progression. Heart failure leads to hypoxia in cells and tissues. Heart failure can be categorized into acute heart failure and chronic heart failure. ![]() Heart failure is a major public health concern because of its high mortality, high rate of hospitalization, and cost of management. Keywords: integrin β3, PTEN/Akt/mTOR, apoptosis, cardiomyocytes, hypoxia Introduction In addition, we found that knockdown of integrin αv or integrin β1 weakened the effect of integrin β3 in cardiomyocyte proliferation.Ĭonclusion: Our findings revealed the molecular mechanism of the role of integrin β3 in cardiomyocyte proliferation and hypoxia-induced cardiomyocyte apoptosis, providing new insights into the mechanisms underlying myocardial protection. We found that integrin β3 promoted cardiomyocytes proliferation through the regulation of the PTEN/Akt/mTOR and ERK1/2 signaling pathways. Furthermore, knocking down integrin β3 expression using shRNA or the integrin β3 inhibitor cilengitide exacerbated cobaltous chloride-induced cardiomyocyte apoptosis, whereas overexpression of integrin β3 weakened cobaltous chloride-induced cardiomyocytes apoptosis. The overexpression of integrin β3 promoted cardiomyocyte proliferation, whereas silencing integrin β3 expression resulted in decreased cell proliferation in vitro. Results: A cobaltous chloride-induced hypoxic microenvironment stimulated cardiomyocyte apoptosis and increased integrin β3 expression in H9C2 cells, AC16 cells, and cardiac tissue from acute and chronic heart failure rats. Confocal microscopy was used to detect the localization of integrin β3 and integrin αv in cardiomyocytes. Flow cytometer was used to investigate the role of integrin β3 in hypoxia-induced cardiomyocyte apoptosis. Western blotting and immunohistochemistry were employed to detect the expression of integrin β3 in the stable cells and rat cardiac tissue. Methods: Stable cells and in vivo acute and chronic heart failure rat models were generated to reveal the essential role of integrin β3 in cardiomyocyte proliferation and apoptosis. Hence, the present investigation aimed to explore the mechanism of integrin β3 in cardiomyocyte proliferation and hypoxia-induced cardiomyocyte apoptosis. However, the exact mechanism by which integrin β3 protects against apoptosis remains unclear. Our previous studies showed that hypoxia induces apoptosis and increases integrin β3 expression in cardiomyocytes. Objective: Integrin β3 is one of the main integrin heterodimer receptors on the surface of cardiac myocytes. Select the file that you have just downloaded and select import option Reference Manager (RIS). Integrin β3 promotes cardiomyocyte proliferation and attenuates hypoxia-induced apoptosis via regulating the PTEN/Akt/mTOR and ERK1/2 pathways. Wei L, Zhou Q, Tian H, Su Y, Fu Gh, Sun T. Hua Tian, MD, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, 25/Ln 2200, Xietu Road, Shanghai 200032, China. ✉ Corresponding authors: Ting Sun, MD, Department of Cardiology, Shanghai Ninth People's Hospital Affiliated with Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. Pathology Center, Shanghai General Hospital/Faculty of Basic Medicine, Shanghai Jiaotong University School of Medicine, No.280, South Chong-Qing Road, Shanghai 200025, People's Republic of China State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 20032, Chinaģ. Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine. Lijiang Wei 1, Qingqing Zhou 2, Hua Tian 2, Yifan Su 1, Guo-hui Fu 3, Ting Sun 1ġ. Research Paper Integrin β3 promotes cardiomyocyte proliferation and attenuates hypoxia-induced apoptosis via regulating the PTEN/Akt/mTOR and ERK1/2 pathways ![]()
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