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Exosomes Pinched from Mesenchymal Stem Cells Overexpressing GATA‐4 Serve as Reservoir for Anti‐apoptotic miRs for Cardioprotection (LB524)
Author(s) -
Yu Bin,
Kim Ha Won,
Wang YiGang,
Ashraf Muhammad,
Xu Meifeng
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb524
Subject(s) - cardioprotection , mesenchymal stem cell , microvesicles , microbiology and biotechnology , exosome , cardiac function curve , microvesicle , apoptosis , microrna , chemistry , transfection , biology , medicine , ischemia , biochemistry , heart failure , gene
There is an abundant evidence that exosomes play an important role in intracellular signaling and exert regulatory function through carrying bioactive molecules. This study is aimed to determine whether cardioprotection by mesenchymal stem cells (MSCs) overexpressing GATA‐4 (MSC GATA‐4 ) is initiated by exosomes which deliver anti‐apoptotic miRs to regulate the target proteins in recipient cells. Exosomes were isolated and purified from MSC GATA‐4 and the control MSCs (MSC Null ). The cell injury was investigated in primary cultured rat neonatal cardiomyocytes (CM) and in rat heart. CM were incubated with exosomes from MSC GATA‐4 (Exo GATA‐4 ) and MSC Null (Exo Null ) under hypoxic environment for 48 hrs. CM survival was significantly increased; the cell apoptosis and LDH release were reduced in CM treated with Exo GATA‐4 compared to Exo Null . Exo GATA‐4 maintained the mitochondrial membrane potential (ΔΨm) CM. Real‐time PCR indicated that the anti‐apoptotic miRs (e.g. miR‐19a and miR‐451) were highly expressed in MSC GATA‐4 and in Exo GATA‐4 . Si‐miR‐19a transfection significantly abolished Exo GATA‐4 mediated cardioprotection. Furthermore, miR‐19 was upregulated and BIM and PTEN were decreased in Exo GATA‐4 treated CM. A rapid internalization of Exo GATA‐4 by CM was observed via time‐lapse images. Direct transplantation of Exo GATA‐4 into the boarder of ischemic myocardium following ligation of left anterior descending coronary artery (LAD) significantly improved cardiac contractile function and reduced infarct size. Exo GATA‐4 were detected inside damaged cells where the expression of miR‐19a was the highest. It is concluded that Exo GATA‐4 mediated cardioprotection through anti‐apoptotic miRs which reduced apoptosis in the ischemic cells. Grant Funding Source : Supported by National Institutes of Health grants HL105176 and HL114654 (M. Xu).