Transplantation of Endothelial Progenitor Cells Overexpressing miR-126-3p Improves Heart Function in Ischemic Cardiomyopathy.

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.

• Authors: Hong Li, Qiang Liu, Ningfu Wang, Yizhou Xu, Lan Kang, Yaqi Ren, Gangjie Zhu
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 82 Issue 9 Pg. 2332-2341 (08 24 2018) ISSN: 1347-4820 [Electronic] Japan
• PMID: 29998929 (Publication Type: Journal Article)

Chemical References

• Cytokines
• MIRN126 microRNA, human
• MicroRNAs

Topics

• Aged
• Aged, 80 and over
• Animals
• Cardiomyopathies (therapy)
• Cell Movement
• Cell Survival
• Cells, Cultured
• Cytokines (metabolism)
• Endothelial Progenitor Cells (transplantation)
• Female
• Humans
• Male
• MicroRNAs (biosynthesis)
• Middle Aged
• Myocardial Infarction (therapy)
• Neovascularization, Physiologic
• Rats
• Rats, Nude
• Ventricular Function, Left