TRAIL protects against endothelial dysfunction in vivo and inhibits angiotensin-II-induced oxidative stress in vascular endothelial cells in vitro

Free Radical Biology & Medicine
Pradeep Manuneedhi CholanMary M Kavurma

Abstract

The vascular endothelium is critical for maintenance of cardiovascular homeostasis. Endothelial dysfunction is a key event of atherosclerosis, with oxidative stress mediated by reactive oxygen species (ROS) playing a major role. Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is increasingly recognised to play a protective role in atherosclerosis, however the molecular mechanisms by which it exerts its beneficial effects are unclear. Here we examined if TRAIL could attenuate vascular oxidative stress and improve endothelial cell (EC) function. In coronary artery disease patients, plasma TRAIL levels were significantly reduced compared to healthy individuals, and negatively correlated with the levels of circulating 8-iso Prostaglandin F2α, a marker of in vivo oxidative stress. In vivo, high-fat fed, atherosclerotic Trail-/-Apoe-/- mice exhibited a significant impairment in endothelial-dependent vasorelaxation, which correlated with increased vascular ROS and 4-hydroxynonenal compared to Apoe-/- mice. Endothelial permeability measured by Evan's blue dye extravasation was increased in several organs of Trail-/- mice compared to wild-type mice, which correlated with a decrease in VE-cadherin expression. In vi...Continue Reading

Citations

Mar 1, 2019·Cardiovascular Research·Megan NashMary M Kavurma
Jun 6, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Siân P CartlandMary M Kavurma
Nov 5, 2019·Frontiers in Pharmacology·Claudio BucoloFilippo Drago
Nov 15, 2019·Molecular and Cellular Biochemistry·Emma HarperPhilip M Cummins
Nov 10, 2020·Journal of Alzheimer's Disease : JAD·Xinquan LiBiao Cai
Nov 3, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Lin-Hua DengWei Liu
Jan 19, 2021·Oxidative Medicine and Cellular Longevity·Aleksandar KibelKristina Selthofer-Relatic
Apr 4, 2021·Journal of Clinical Medicine·Katarzyna KakarekoTomasz Hryszko
May 30, 2020·Cancer Cell·Matthew T WitkowskiIannis Aifantis

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