Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
Ischemic Heart Disease
Transplantation of Endothelial Progenitor Cells Overexpressing miR-126-3p Improves Heart Function in Ischemic Cardiomyopathy
Hong LiQiang LiuNingfu WangYizhou XuLan KangYaqi RenGangjie Zhu
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2018 Volume 82 Issue 9 Pages 2332-2341

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Abstract

Background: In a previous study, a low level of miR-126-3p in endothelial progenitor cells (EPCs) was linked to the outcome of ischemic cardiomyopathy (ICM) patients. However, it remains unclear whether transplantation with miR-126-3p-overexpressing EPCs (MO-EPCs) can improve the cardiac function of ICM animal models.

Methods and Results: miR-126-3p overexpression by lentiviral vector significantly increased migration and tube-like structures of EPCs from ICM patients. MO-EPCs or non-modified EPCs (NM-EPCs) were transplanted into nude rats with ICM induced by coronary artery ligation. MO-EPC transplantation increased capillary density and EPC survival rate in myocardial tissues of nude rats. Cytokines were also assessed by antibody array and real-time RT-PCR. G-CSF, VEGF-A, IL-3, IL-10, IGF-1, angiogenin, HGF, TIMP-1 and TIMP-2 were upregulated, and IL-8, MCP-1, MCP-2, TNF-α, TNF-β and MIP-1β were downregulated after miR-126-3p overexpression in EPCs. The same results were obtained in infarction tissues of nude rats after MO-EPC transplantation. Eight weeks after MO-EPC transplantation, left ventricular function improved significantly with clearly decreased infarction size, increased anterior wall thickness, and inhibition of inflammation compared with the results for NM-EPC transplantation. However, MO-EPC transplantation showed no increase in survival time of nude rats with ICM during 8 weeks of observation.

Conclusions: miR-126-3p can restore the biology of EPCs from ICM patients. Moreover, MO-EPC transplantation improves cardiac function effectively, representing a promising future treatment for ICM.

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© 2018 THE JAPANESE CIRCULATION SOCIETY
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