Apolipoprotein A-1 mimetic peptide 4F promotes endothelial repairing and compromises reendothelialization impaired by oxidized HDL through SR-B1

Redox Biology

卷:15

Y. Eugene Chen¹  Subramaniam Pennathur¹  Anna V. Mathew¹  Huiyong Yin²  Yuan He³  Belinda Willard⁴  Mingming Zhao⁵  Lemin Zheng⁵  Chenguang Niu⁵  Liang Ji⁵  Baoqi Yu⁵  Bing Pan⁵  Dan He⁵  Congying Wu⁶  Jingru Jin⁷  Wenjing Zhang⁷ 

[1] Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA;

[2] Key Laboratory of Food Safety Research, Institute for Nutritional Sciences (INS), Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200031, China;

[3] National Research Institute for Health and Family Planning, Beijing 100081, China;

[4] Proteomics Laboratory, Cleveland Clinic, Cleveland, OH 44195, USA;

[5] The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Health Science Center, Peking University, Beijing 100191, China;

[6] The Institute of Systems Biomedicine, Department of Medical Genetics, Peking University Health Science Center, Beijing 100191, China;

[7] The Military General Hospital of Beijing, Beijing 100700, China;

关键词: ApoA-1;    4F;    Endothelial repair;    Oxidized HDL;    Re-endothelialization;   

DOI  :  10.1016/j.redox.2017.11.027

来源: DOAJ

【 摘 要 】

Disruption of endothelial monolayer integrity is the primary instigating factor for many cardiovascular diseases. High density lipoprotein (HDL) oxidized by heme enzyme myeloperoxidase (MPO) is dysfunctional in promoting endothelial repair. Apolipoprotein A-1 mimetic 4F with its pleiotropic benefits has been proven effective in many in vivo models. In this study we investigated whether 4F promotes endothelial repair and restores the impaired function of oxidized HDL (Cl/NO2-HDL) in promoting re-endothelialization. We demonstrate that 4F and Cl/NO2-HDL act on scavenger receptor type I (SR-B1) using human aorta endothelial cells (HAEC) and SR-B1 (-/-) mouse aortic endothelial cells. Wound healing, transwell migration, lamellipodia formation and single cell migration assay experiments show that 4F treatment is associated with a recovery of endothelial cell migration and associated with significantly increased endothelial nitric oxide synthase (eNOS) activity, Akt phosphorylation and SR-B1 expression. 4F increases NO generation and diminishes oxidative stress. In vivo, 4F can stimulate cell proliferation and re-endothelialization in the carotid artery after treatment with Cl/NO2-HDL in a carotid artery electric injury model but fails to do so in SR-B1(-/-) mice. These findings demonstrate that 4F promotes endothelial cell migration and has a potential therapeutic benefit against early endothelial injury in cardiovascular diseases.

【 授权许可】

Unknown