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Erythropoietin promotes myocardial infarction repair in mice by improving the function of Sca-1+ stem cells

ZUO Lin¹, LI Duan-Duan¹, MA Xiu-Xia¹, SHI Shan-Hui¹, LYU Ding-Chao², SHEN Jing¹, ZHANG Wei-Fang³, GAO Er-He⁴, CAO Ji-Min^1,*

¹Key Laboratory of Cellular Physiology, Ministry of Education, and the Department of Physiology, School of Basic Sciences, Shanxi Medical University, Taiyuan 030001, China；²Department of Cardiology, the People’s Hospital of Changzhi City, Changzhi 046000, China；³Center for Functional Experiments, Shanxi Medical University, Taiyuan 030001, China；⁴Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA

Abstract

Myocardial infarction (MI) is one of the leading causes of death in the world. With the improvement of clinical therapy, the mortality of acute MI has been significantly reduced. However, as for the long-term impact of MI on cardiac remodeling and cardiac function, there is no effective prevention and treatment measures. Erythropoietin (EPO), a glycoprotein cytokine essential to hematopoiesis, has anti-apoptotic and pro-angiogenetic effects. Studies have shown that EPO plays a protective role in cardiomyocytes in cardiovascular diseases, such as cardiac ischemia injury and heart failure. EPO has been demonstrated to protect ischemic myocardium and improve MI repair by promoting the activation of cardiac progenitor cells (CPCs). This study aimed to investigate whether EPO can promote MI repair by enhancing the activity of stem cell antigen 1 positive stem cells (Sca-1+ SCs). Darbepoetin alpha (a long-acting EPO analog, EPOanlg) was injected into the border zone of MI in adult mice. Infarct size, cardiac remodeling and performance, cardiomyocyte apoptosis and microvessel density were measured. Lin− Sca-1+ SCs were isolated from neonatal and adult mouse hearts by magnetic sorting technology, and were used to identify the colony forming ability and the effect of EPO, respectively. The results showed that, compared to MI alone, EPOanlg reduced the infarct percentage, cardiomyocyte apoptosis ratio and left ventricular (LV) chamber dilatation, improved cardiac performance, and increased the numbers of coronary microvessels in vivo. In vitro, EPO increased the proliferation, migration and clone formation of Lin− Sca-1+ SCs likely via the EPO receptor and downstream STAT-5/p38 MAPK signaling pathways. These results suggest that EPO participates in the repair process of MI by activating Sca-1+ SCs.

Key words: Myocardial infarction; erythropoietin; stem cells; mice; cell migration

Received: 　　Accepted:

Corresponding author: 曹济民　　E-mail:

DOI: 10.13294/j.aps.2023.0013

Citing This Article：

ZUO Lin, LI Duan-Duan, MA Xiu-Xia, SHI Shan-Hui, LYU Ding-Chao, SHEN Jing, ZHANG Wei-Fang, GAO Er-He, CAO Ji-Min. Erythropoietin promotes myocardial infarction repair in mice by improving the function of Sca-1+ stem cells. Acta Physiol Sin 2023; 75 (1): 36-48