Cardiac stem cells with electrical stimulation improve ischaemic heart function through regulation of connective tissue growth factor and miR-378

Sun Wook Kim, Ha Won Kim, Wei Huang, Motoi Okada, Jeffrey A. Welge, Yigang Wang, Muhammad Ashraf

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Aims: In this study, we investigated whether pre-conditioning (PC) by electrical stimulation (EleS) induces cytoprotective effect on cardiac stem cells (CSCs) and determined its underlying molecular mechanisms. Methods and results: Sca-1+ CSCs were isolated from male C57BL6 mice (12 weeks) hearts. PC of CSCs with EleS (EleSCSCs) was carried out for 3 h at 1.5 V followed by exposure to 300 μM H2O2 for 5 h. Cytoprotective effects and cell adhesion ability were significantly increased by EleS as evaluated by transferase-mediated dUTP nick-end labelling (TUNEL), lactate dehydrogenase (LDH) release assay, and adhesion assay. EleS increased phosphorylation of AKT, focal adhesion kinase (FAK), and glycogen synthase kinase (GSK3β), as well as decreased caspase-3 cleavage. Interestingly, inhibition of AKT or FAK abolished the pro-survival effects of EleS. We found that connective tissue growth factor (Ctgf) was responsible for EleS-induced CSC survival and adhesion. The survival rate of EleSCSCs after transplantation in the infarcted myocardium was significantly increased together with improvement in cardiac function. Importantly, knockdown of Ctgf abolished EleS-induced cytoprotective effects and recovery of cardiac function. Furthermore, we identified miR-378 as a potential Ctgf regulator in EleSCSCs. Conclusion: EleS enhanced CSC survival in vitro and in vivo as well as functional recovery of the ischaemic heart through an AKT/FAK/CTGF signalling pathway. It is suggested that Ctgf and miR-378 are novel therapeutic targets for stem cell-based therapy.

Original languageEnglish (US)
Pages (from-to)241-251
Number of pages11
JournalCardiovascular Research
Volume100
Issue number2
DOIs
Publication statusPublished - Nov 1 2013

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Keywords

  • CTGF
  • Electrical stimulation
  • Ischaemic heart
  • Survival
  • miR-378

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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