Extracorporeal shock wave stimulates expression of the angiogenic genes via mechanosensory complex in endothelial cells: Mimetic effect of fluid shear stress in endothelial cells
Extracorporeal shock wave stimulates expression of the angiogenic genes via mechanosensory complex in endothelial cells: Mimetic effect of fluid shear stress in endothelial cells
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DOI：
10.1016/j.ijcard.2013.07.112
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发表时间：
2013-10-09
影响因子：
3.5
通讯作者：
Kwon, Kihwan
中科院分区：
文献类型：
--
作者：
Ha, Chang Hoon;Kim, Sunghyen;Kwon, Kihwan
背景：体外冲击波已被用于多种疾病的无创治疗，包括肌肉骨骼疾病。特别是低能量激波具有抗炎作用，能促进缺血组织血管生成。然而，内皮信号传导的详细细胞通路尚不完全清楚。我们通过比较内皮细胞的层流剪切应力和振荡剪切应力，探讨低能量激波在血管生成基因表达中的作用及其分子机制。方法和结果：我们发现低能量（0.012-0.045 mJ/mm(2)）的激波刺激Akt、eNOS和Erk 1/2的磷酸化具有时间依赖性，类似于层流剪切应力的作用。转染内皮细胞编码VEGFR2、VE-cadherin和PECAM-1的siRNA可抑制冲击波诱导的Akt、eNOS和Erk 1/2磷酸化和血管生成基因（包括Akt、eNOS、KLF2/4和Nur77）的表达。此外，机械刺激通过体外冲击波诱导内皮细胞迁移和管的形成。结论：我们的研究结果表明，冲击波诱导的Akt/eNOS磷酸化和血管生成基因表达是通过涉及VEGFR-2、VE-cadherin和PECAM-1的机械感觉复合物的形成介导的，其作用类似于层流剪切应力的作用。2013爱思唯尔爱尔兰有限公司版权所有。
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/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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.