Redox Biology (May 2018)

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

  • Dan He,
  • Mingming Zhao,
  • Congying Wu,
  • Wenjing Zhang,
  • Chenguang Niu,
  • Baoqi Yu,
  • Jingru Jin,
  • Liang Ji,
  • Belinda Willard,
  • Anna V. Mathew,
  • Y. Eugene Chen,
  • Subramaniam Pennathur,
  • Huiyong Yin,
  • Yuan He,
  • Bing Pan,
  • Lemin Zheng

DOI
https://doi.org/10.1016/j.redox.2017.11.027
Journal volume & issue
Vol. 15, no. C
pp. 228 – 242

Abstract

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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.

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