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GW23-e0920
EFFECTS OF PHD2 ON PARACRINE EFFECT OF ADIPOSE DERIVED MESENCHYMAL STEM CELLS MEDIATED CARDIOPROTECTION
  1. Wei Wang,
  2. Chunyu Zeng
  1. Department of Cardiology, Chongqing Institute of Cardiovascular Disease, Daping Hospital, Third Military Medical University, Chongqing

    Abstract

    Objectives To determine the roles of prolyl hydroxylase 2 (PHD2) RNA interference on the adipose-derived mesenchymal stem cells (ADSCs)-mediated paracrine effect against myocardial injury and to study its mechanism.

    Methods ADSCs of passage 3 were transfected with lentiviral knockdown of PHD2. We established a superoxide damage model in vitro by treating neonatal rat ventricular myocytes (NRVMs) with hydrogen peroxide (H2O2, 100 mM) for 6 h. Conditioned medium (CM) of ADSCs was collected for pretreating NRVM. The cell apoptosis was detected by TUNEL staining and caspase-3 protein expression. Prosurvival cytokines VEGF、HGF and IGF-1 secreted by ADSCs were determined by ELISA kit.

    Results shPHD2-GFP-ADSC-CM significantly attenuated the apoptosis of NRVM, TUNEL positive rate decreased 30.3% and caspase-3 protein expression decreased 24.8%, comparing with GFP-ADSC-CM. Prosurvival cytokine IGF-1 in shPHD2-GFP-ADSC-CM significantly increased compared with GFP-ADSC-CM. The anti-apoptotic effect of shPHD2-GFP-ADSC-CM was largely blocked by neutralisation IGF-1.

    Conclusions PHD2 inhibition of ADSCs enhances the paracrine-mediated myocardial protection, which may be associated with increased secretion of prosurvival cytokine IGF-1.

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