Paracrine effects of mir-210-3p on angiogenesis in hypoxia-treated c-kit-positive cardiac cells

Abstract

AbstractObjective: Treatment with c-kit-positive cardiac cells (CPCs) has been shown to improve the prognosis of ischemic heart disease. MicroRNAs (miRNAs) confer protection by enhancing the cardiac repair process, but their specific functional mechanisms remain unclear. This study aimed to screen for differentially expressed miRNAs in CPCs under hypoxia and explore their effects on the function of CPCs.Methods: We harvested CPCs from C57 adult mice and later performed a high-throughput miRNA sequencing for differential expression profiling analysis. Subsequently, we intervened with the differentially expressed gene miR-210-3p in CPCs and detected changes in the secretion of angiogenesis-related factors through a protein-chip analysis. Finally, we applied CPC supernatants of different groups as conditioned medium to treat mouse cardiac microvascular endothelial cells (CMECs) and further investigated the functional effects of miR-210-3p on c-kit+CPCs under ischemia and hypoxia conditions.Results: The miR-210-3p was highly increased in hypoxia-treated CPCs. Protein-chip detection revealed that CPCs expressed cytokines such as FGF basic, angiogenin, and vascular endothelial growth factor (VEGF) and that hypoxia enhanced their release. Silencing miR-210-3p resulted in a reduction in the release of these angiogenesis-related factors. In addition, the conditioned medium of hypoxia-treated CPCs promoted the proliferation, migration, and tube-forming capabilities of CMECs. In contrast, the conditioned media of CPCs with silenced miR-210-3p after hypoxia decreased the proliferation, migration, and tube-forming ability of CMEC.Conclusions: The CPCs exert proangiogenic effects via paracrine pathways mediated by miR-210-3p. Upregulation of miR-210-3p in hypoxia-treated CPCs may enhance their paracrine function by regulating the secretion of angiogenic factors, thereby promoting angiogenesis in ischemic heart disease.

Keywords

• c-kit-positive cardiac cells
• hypoxia
• miR-210-3p
• paracrine functions
• ischemic cardiomyopathy