Cardiac protection of prostacyclin secreted from endothelial progenitor cells against oxidative stress-induced apoptosis: verified by cardiac electrophysiological tests

doi:10.3969/j.issn.2095-4344.2016.20.009

Abstract

Abstract:

BACKGROUND: Prostacyclin (PGI2) and its analogs have been reported to prevent pressure overload-induced cardiac hypertrophy, and to reduce cardiac ischemia/reperfusion injury. However, clinical application of PGI2 is challenging due to its short half-life (< 2 minutes). Thus, we have generated PGI2 expressing rat endothelial progenitor cell strains (PGI2-EPCs) that constitutively secrete prostacyclin.
OBJECTIVE: To investigate the protective effect of PGI2-EPCs against oxidative stress-induced cardiomyocyte injury.
METHODS: Cultured H9c2 cells in vitro were assigned into four groups: H9c2 cells treated by H2O2 for 4 hours. H9c2 cells were pretreated by conditioned medium (collected form EPCs and PGI2-EPCs or collected form EPCs and PGI2-EPCs mixed with native EPCs) before the addition of H2O2. PBS instead of conditioned mediums served as negative control. The paracrine effect of PGI2-EPCs on in vitro angiogenesis of native EPCs was evaluated. MTT and Hoechst 33342 assays were used to examine the protective effect of conditioned medium on H2O2-induced rat embryonic cardiomyocyte apoptosis and cell viability. Finally, the effect of conditioned medium on the electric activities of adult cardiomyocytes was measured by whole-cell patch clamp techniques.
RESULTS AND CONCLUSION: When native EPCs mixed with conditioned medium of PGI2-EPCs, the total length of tubes was significantly longer compared with those mixed with CM of EPC. Rat embryonic cardiomyocytes pretreated with conditioned medium of PGI2-EPCs significantly reduced H2O2-induced apoptosis and preserved cell viability compared with pretreatment with EPC-conditioned medium and without pretreatment (P < 0.01). Pretreatment of rat adult cardiomyocytes with conditioned medium of PGI2-EPCs abolished H2O2-induced early after depolarization and shortened H2O2-induced action potential duration prolongation (P < 0.01) towards baseline. Our findings indicate that PGI2-EPCs protect against oxidative stress-induced cardiomyocyte injury through paracrine action. This Study provides the groundwork for an innovative cell therapy approach to treat ischemic heart disease.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Prostaglandins I, Myocardium, Tissue Engineering

CLC Number:

R318

Zhang Jing, Ruan Lu, Kang Li, Cui Xiao-hai, Zhang Jia. Cardiac protection of prostacyclin secreted from endothelial progenitor cells against oxidative stress-induced apoptosis: verified by cardiac electrophysiological tests[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(20): 2949-2956.

Figures/Tables 1

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