title: Extracorporeal shock wave stimulates expression of the angiogenic genes via mechanosensory complex in endothelial cells: mimetic effect of fluid shear stress in endothelial cells.
abstract: BACKGROUND
  Extracorporeal shock wave has been used in the noninvasive treatment of various diseases including musculoskeletal disorders. In particular, shock wave with low energy level showed anti-inflammatory effect and increased angiogenesis in ischemic tissues. However, the detailed cellular pathway in endothelial signaling is not fully understood. We investigate the role of shock wave with low energy level in angiogenic gene expression and underlying molecular mechanism by comparing the laminar and oscillatory fluid shear stresses in endothelial cells.
  
  
  RESULTS
  We show that shock wave with low energy level (0.012-0.045 mJ/mm(2)) stimulated phosphorylation of Akt, eNOS and Erk 1/2 in a time-dependent manner which is similar to the effect of laminar fluid shear stress. The transfection of endothelial cells with siRNA encoding VEGFR2, VE-cadherin and PECAM-1 inhibited shock wave-induced phosphorylation of Akt, eNOS and Erk 1/2 and angiogenic gene expressions, including Akt, eNOS, KLF2/4, and Nur77. Moreover, mechanical stimulation through extracorporeal shock wave induced endothelial cell migration and tube formation.
  
  
  CONCLUSIONS
  Our results demonstrate that shock wave-induced Akt/eNOS phosphorylation and angiogenic gene expression were mediated through the mechanosensory complex formation involving VEGFR-2, VE-cadherin and PECAM-1 which was similar to the effect of laminar shear stress.
authors.affiliation: Medical Research Institute, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea.
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Ha
authors.forename: Sunghyen
authors.initials: S
authors.lastname: Kim
authors.forename: Jihwa
authors.initials: J
authors.lastname: Chung
authors.forename: Shung Hyen
authors.initials: SH
authors.lastname: An
authors.forename: Kihwan
authors.initials: K
authors.lastname: Kwon
mesh_terms: D042501:Angiogenic Proteins / Q000096:biosynthesis*; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D019220:High-Energy Shock Waves; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology; D006801:Humans; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008560:Membrane Fluidity / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D033081:Shear Strength / Q000502:physiology*
chemical_list: D042501:Angiogenic Proteins
keywords: Angiogenesis; Endothelial cells; Extracorporeal shock wave; Fluid shear stress; Gene expression; Mechanosensory complex formation