Activation of SHH signaling pathway promotes vasculogenesis in post-myocardial ischemic-reperfusion injury

Int J Clin Exp Pathol. 2015 Oct 1;8(10):12464-72. eCollection 2015.

Abstract

This study aimed to investigate the potential roles of sonic Hedgehog (SHH) expression in vasculogenesis in post-myocardial ischemic-reperfusion injury (MIRI) and its underlying mechanism. Cardiac microvascular endothelial cells (CMECs) isolated from the SD rat hearts tissues were used to construct the MIRI model. mRNA level of SHH in control cells and MIRI cells was detected using RT-PCR analysis. Furthermore, effects of SHH expression on CMECs viability and apoptosis were analyzed using MTT assay and Annexin-V-FITC kit respectively. Moreover, effects of SHH expression on the pathway signal proteins expression was analyzed using ELISA and western blotting. mRNA level of SHH was significantly decreased compared to the controls (P<0.05). Besides, CMECs viability was significantly increased while cell apoptosis was decreased by SHH application compared with the controls (P<0.05). Vasculogenesis-related factors including VEGF, FGF and Ang were significantly increased by SHH application, as well as the SHH signal proteins including Patch-1, Gli1, Gli2 and SMO (P<0.05). However, these effects of SHH application on biological factors levels were reversed by the SHH inhibitor application. This study suggested that SHH over expression may play a pivotal contribute role in vasculogenesis through activating the SHH signals in post-MIRI.

Keywords: Myocardial ischemic-reperfusion injury; SHH; cell apoptosis; cell viability; vasculogenesis.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Blotting, Western
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Hedgehog Proteins / metabolism*
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / physiopathology
  • Myocardial Reperfusion Injury / metabolism*
  • Myocardial Reperfusion Injury / physiopathology
  • Neovascularization, Physiologic / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / physiology*

Substances

  • Hedgehog Proteins
  • Shh protein, rat