TY - JOUR
T1 - Extracorporeal shock wave stimulates expression of the angiogenic genes via mechanosensory complex in endothelial cells
T2 - Mimetic effect of fluid shear stress in endothelial cells
AU - Ha, Chang Hoon
AU - Kim, Sunghyen
AU - Chung, Jihwa
AU - An, Shung Hyen
AU - Kwon, Kihwan
N1 - Funding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( NRF-2011-0009474 ).
PY - 2013/10/9
Y1 - 2013/10/9
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Endothelial cells
KW - Extracorporeal shock wave
KW - Fluid shear stress
KW - Gene expression
KW - Mechanosensory complex formation
UR - http://www.scopus.com/inward/record.url?scp=84886306197&partnerID=8YFLogxK
U2 - 10.1016/j.ijcard.2013.07.112
DO - 10.1016/j.ijcard.2013.07.112
M3 - Article
C2 - 23915523
AN - SCOPUS:84886306197
VL - 168
SP - 4168
EP - 4177
JO - International Journal of Cardiology
JF - International Journal of Cardiology
SN - 0167-5273
IS - 4
ER -