Apolipoprotein A-1 mimetic peptide 4F promotes endothelial repairing and compromises reendothelialization impaired by oxidized HDL through SR-B1.
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.
['He|Dan|D|', 'Zhao|Mingming|M|', 'Wu|Congying|C|', 'Zhang|Wenjing|W|', 'Niu|Chenguang|C|', 'Yu|Baoqi|B|', 'Jin|Jingru|J|', 'Ji|Liang|L|', 'Willard|Belinda|B|', 'Mathew|Anna V|AV|', 'Chen|Y Eugene|YE|', 'Pennathur|Subramaniam|S|', 'Yin|Huiyong|H|', 'He|Yuan|Y|', 'Pan|Bing|B|', 'Zheng|Lemin|L|']
D000818:Animals D001011:Aorta D002465:Cell Movement D049109:Cell Proliferation D042783:Endothelial Cells D004730:Endothelium, Vascular D006801:Humans D008075:Lipoproteins, HDL D051379:Mice D009569:Nitric Oxide D052250:Nitric Oxide Synthase Type III D018384:Oxidative Stress D010455:Peptides D009195:Peroxidase D010766:Phosphorylation D051122:Scavenger Receptors, Class B
4F Endothelial repair Oxidized HDL Re-endothelialization ApoA-1