Key result
ACE2-overexpressing MSCs reduce infarct size and cardiac fibrosis while improving function after MI.
Why the study?
The effect of ACE2-overexpressed mesenchymal stem cells on myocardial infarction remained unexplored.
Does transplantation of ACE2-overexpressed mesenchymal stem cells improve cardiac function and reduce infarct size in a rat model of myocardial infarction?
Does transplantation of ACE2-overexpressed mesenchymal stem cells improve cardiac function and reduce infarct size in a rat model of myocardial infarction?
ACE2 overexpression enhances the therapeutic efficacy of mesenchymal stem cells in myocardial infarction by improving the local microenvironment, promoting angiogenesis, and preserving cardiac function.
Background Angiotensin-converting enzyme-2 (ACE2) overexpression improves left ventricular remodeling and function in diabetic cardiomyopathy; however, the effect of ACE2-overexpressed mesenchymal stem cells (MSCs) on myocardial infarction (MI) remains unexplored. This study aimed to investigate the effect of ACE2-overexpression on the function of MSCs and the therapeutic efficacy of MSCs for MI. Methods MSCs were transfected with Ace2 gene using lentivirus, and then transplanted into the border zone of ischemic heart. The renin-angiotensin system (RAS) expression, nitric oxide synthase (NOS) expression, paracrine factors, anti-hypoxia ability, tube formation of MSCs, and heart function were determined. Results MSCs expressed little ACE2. ACE2-overexpression decreased the expression of AT1 and VEGF apparently, up-regulated the paracrine of HGF, and increased the synthesis of Angiotensin 1-7 in vitro. ACE2-overexpressed MSCs showed a cytoprotective effect on cardiomyocyte, and an interesting tube formation ability, decreased the heart fibrosis and infarct size, and improved the heart function. Conclusion Therapies employing MSCs with ACE2 overexpression may represent an effective treatment for improving the myocardium microenvironment and the cardiac function after MI.
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Liu et al. (2020) studied Myocardial infarction (rat model) (n=20). ACE2-overexpressed mesenchymal stem cells (LV-ACE2-MSCs) vs. DMEM without cells (vehicle) or control mesenchymal stem cells (LV-GFP-MSCs) was evaluated on Cardiac function (ejection fraction and fractional shortening), infarct size, and cardiac fibrosis at 30 days. Transplantation of ACE2-overexpressed mesenchymal stem cells into the border zone of ischemic hearts significantly decreased cardiac fibrosis and infarct size, and improved cardiac function compared to vehicle or control MSCs.
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