Abstract 9788: Exosomes Released From GATA-4 Overexpressed Mesenchymal Stem Cells Enrich Anti-apoptotic microRNAs and Mediate Cardioprotection

Abstract

Increased evidences indicate that exosomes play an important role in cell to cell communication and exert regulatory function by shuttling bioactive molecules. We have previously reported that overexpression of GATA-4 in mesenchymal stem cells (MSC) (MSC GATA-4 ) increased cardioprotection. In this study, we investigated if this action was associated with microRNAs (miRs) carried by exosomes. Our studies indicated: 1) Exosomes isolated from MSC increased cultured neonatal cardiomyocyte (CM) survival under hypoxic environment for 48 hours in a concentration-dependent manner (Fig. A). The cardioprotection was partially attenuated by treating MSC with GW4869 (10μM), an exosome release inhibitor and enhanced in the exosomes obtained from MSC GATA-4 (Exo GATA-4 ) (Fig. B). 2) Exo GATA-4 well maintained mitochondria membrane potential of CM assessed by JC-1 staining and expressed as a ratio of aggregate to monomer fluorescence (Fig. C). 3) The expression of pro-apoptotic miR-15b, miR-34c in CM was up-regulated, and anti-apoptotic miR-19a, miR-451 was down-regulated following exposure to hypoxia (Fig. D). 4) The expression of miR-19a and miR-451 was higher in MSC GATA-4 (Fig. E) and Exo GATA-4 (Fig. F). 5) Treatment CM with Exo GATA-4 dramatically reversed the alteration of these miRs in CM which was induced by exposure to hypoxia and resulted in an increase of expression of miR-19a and miR-451 (Fig. G). It is concluded that GATA-4 enhanced MSC mediated cardioproteciton, which was associated with a transfer of exosomes enriched anti-apoptotic miRs from MSC to CM.