title: Cardiac shock wave therapy attenuates H9c2 myoblast apoptosis by activating the AKT signal pathway.
abstract: BACKGROUND
  Previous studies have demonstrated that Cardiac Shock Wave Therapy (CSWT) improves myocardial perfusion and cardiac function in a porcine model of chronic myocardial ischemia and also ameliorates myocardial ischemia in patients with severe coronary artery disease (CAD). Apoptosis plays a key role in ischemic myocardial pathogenesis. However, it remains unclear whether CSWT is beneficial for ischemia/hypoxia (I/H)-induced myocardial cell apoptosis and by which mechanism CSWT could improve heart function. We put forward the hypothesis that CSWT might protect heart function during ischemia/hypoxia by decreasing apoptosis.
  
  
  METHODS
  We generated ischemia/hypoxia (I/H)-induced apoptosis in the H9c2 myoblast cell line to examine the CSWT function and possible mechanisms. H9c2 cells were treated under hypoxic serum-starved conditions for 24 h and then treated with or without CSWT (500 shots, 0.06, 0.09, 0.12mJ/mm(2)). The apoptotic cell rate was determined by flow cytometry assay, cell viability was examined by the MTT assay, nuclear fragmentation was detected by Hoechst 33342 staining, and the mitochondrial-mediated intrinsic pathway of apoptosis was assessed by the expression of Bax and Bcl-2 protein and Caspase3 activation.
  
  
  RESULTS
  First, apoptosis could be induced by ischemia/hypoxia in H9c2 cells. Second, CSWT attenuates the cell death and decreases the H9c2 cell apoptosis rate induced by ischemia and hypoxia. Third, CSWT suppresses the expression of apoptosis molecules that regulate the intrinsic pathway of apoptosis in H9c2 cells. Fourth, CSWT increases the phosphorylation of AKT, which indicates the activation of the PI3K-AKT pathway.
  
  
  CONCLUSIONS
  These results indicate that CSWT exerts a protective effect against I/H-induced cell death, potentially by preventing the activation of components of the mitochondrial-dependent intrinsic apoptotic pathway. We also demonstrate that the PI3K-Akt pathway may be involved in the CSWT effects on apoptosis.
authors.affiliation: Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yu
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.forename: Baoyi
authors.initials: B
authors.lastname: Liu
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Dapeng
authors.initials: D
authors.lastname: Dai
authors.forename: Jianping
authors.initials: J
authors.lastname: Cai
authors.forename: Qing
authors.initials: Q
authors.lastname: He
mesh_terms: D000818:Animals; D017209:Apoptosis; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D012780:Short-Wave Therapy; D015398:Signal Transduction
chemical_list: D051057:Proto-Oncogene Proteins c-akt