Atorvastatin plus therapeutic ultrasound improve postnatal neovascularization in response to hindlimb ischemia via the PI3K-Akt pathway

American Journal of Translational Research

Rui-Lin Li¹  Xue-Lian Wang²  Yi-Qin Shi³  Jia Qi⁴  Zhao-Yang Lu⁵ 

[1] Department of Central Laboratory, Tenth Peoples Hospital of Tongji University, Yanchang Road 301, Shanghai 200072, China;Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University, Kongjiang Road 1665, Shanghai 200092, China;Department of Nephrology, Zhongshan Hospital, Fudan University, Fenglin Road 180, Shanghai 200032, China;Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University, Kongjiang Road 1665, Shanghai 200092, China;Shanghai Acoustics Laboratory, Chinese Academy of Science, Xinlai Road 399, Shanghai 200032, China

关键词: Statin;    therapeutic ultrasound;    angiogenesis;    eNOS;    VEGF;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Statins and therapeutic ultrasound (TUS) have been shown to ameliorate angiogenesis on ischemic hindlimb animals and promote human umbilical vein endothelial cells (HUVECs) tube formation and proliferation. Here, we evaluate the therapeutic effect of TUS in combination with atorvastatin (Ator) therapy on angiogenesis in hindlimb ischemia and HUVECs. After subjecting excision of the left femoral artery, all mice were randomly distributed to one of four groups: Control; Ator treated mice (Ator); TUS treated mice (TUS); and Ator plus TUS treated mice (Ator+TUS). At day 14 post-surgery, the Ator plus TUS treatment cohort had the greatest blood perfusion, accompanied by elevated capillary density. In vitro, Ator plus TUS augmented tube formation, migration and proliferative capacities of HUVECs. Additionally, the united administration upregulated expression of angiogenic factors phosphorylated Akt (p-Akt), phosphorylated endothelial nitric oxide synthase (p-eNOS), as well as vascular endothelial growth factor (VEGF), both in vivo and in vitro. These benefits could be blocked by either phosphoinositide 3-kinase (PI3K) or eNOS inhibitor. Our data indicated that the united administration could significantly enhance ischemia-mediated angiogenesis and exert a protective effect against ischemic/hypoxia induced damage among HUVECs through up-regulating VEGF expression and activating the PI3K-Akt-eNOS pathway.

【 授权许可】

CC BY-NC