Cardiac protection of prostacyclin secreted from endothelial progenitor cells against oxidative stress-induced apoptosis：verified by cardiac electrophysiological tests
10.3969/j.issn.2095-4344.2016.20.009
- VernacularTitle:前列腺素I2-内皮祖细胞保护氧化应激受损心肌细胞凋亡：心肌电生理验证
- Author:
Jing ZHANG
;
Lu RUAN
;
Li KANG
;
Xiaohai CUI
;
Jia ZHANG
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2016;20(20):2949-2956
- CountryChina
- Language:Chinese
-
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 chalenging due to its short half-life (< 2 minutes). Thus, we have generated PGI2 expressing rat endothelial progenitor cel strains (PGI2-EPCs) that constitutively secrete prostacyclin.
OBJECTIVE:To investigate the protective effectof PGI2-EPCs against oxidative stress-induced cardiomyocyte injury.
METHODS:Cultured H9c2 celsin vitrowere assigned into four groups: H9c2 cels treated by H2O2for 4 hours. H9c2 cels were pretreated by conditioned medium (colected form EPCs and PGI2-EPCs or colected 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 onin 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 cel viability. Finaly, the effect of conditioned medium on the electric activities of adult cardiomyocyteswas measuredby whole-cel 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 cel viability compared with pretreatment with EPC-conditioned medium and without pretreatment (P< 0.01). Pretreatment of rat adult cardiomyocyteswith conditioned medium of PGI2-EPCs abolished H2O2-induced early afterdepolarization and shortened H2O2-induced action potential duration prolongation (P< 0.01) towards baseline.Our findings indicate thatPGI2-EPCs protect against oxidative stress-induced cardiomyocyte injury through paracrine action.ThisStudy providesthe groundwork for an innovative cel therapy approach to treat ischemic heart disease.
