Extracorporeal shock wave stimulates expression of the angiogenic genes via mechanosensory complex in endothelial cells: Mimetic effect of fluid shear stress in endothelial cells

Chang Hoon Ha, Sunghyen Kim, Jihwa Chung, Shung Hyen An, Kihwan Kwon

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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. Methods and results We show that shock wave with low energy level (0.012-0.045 mJ/mm2) 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.

Original languageEnglish
Pages (from-to)4168-4177
Number of pages10
JournalInternational Journal of Cardiology
Volume168
Issue number4
DOIs
StatePublished - 9 Oct 2013

Keywords

  • Angiogenesis
  • Endothelial cells
  • Extracorporeal shock wave
  • Fluid shear stress
  • Gene expression
  • Mechanosensory complex formation

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