Endothelial microparticle-derived reactive oxygen species: role in endothelial signaling and vascular function

Burger, D., Turner, M., Munkonda, M. N. and Touyz, R. M. (2016) Endothelial microparticle-derived reactive oxygen species: role in endothelial signaling and vascular function. Oxidative Medicine and Cellular Longevity, 2016, 5047954. (doi: 10.1155/2016/5047954) (PMID:27313830) (PMCID:PMC4893592)

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Endothelial microparticles are effectors of endothelial damage; however mechanisms involved are unclear. We examined the effects of eMPs on cultured endothelial cells (ECs) and isolated vessels and investigated the role of eMP-derived reactive oxygen species (ROS) and redox signaling in these processes. eMPs were isolated from EC media and their ability to directly produce ROS was assessed by lucigenin and liquid chromatography. Nicotinamide adenine dinucleotide phosphate oxidase (Nox) subunits were probed by Western blot. ECs were treated with eMPs and effects on kinase signaling, superoxide anion (O2 ∙−) generation, and nitric oxide (NO) production were examined. Acetylcholine-mediated vasorelaxation was assessed by myography in eMP-treated mesenteric arteries. eMPs contained Nox1, Nox2, Nox4, p47phox, p67phox, and p22phox and they produced ROS which was inhibited by the Nox inhibitor, apocynin. eMPs increased phosphorylation of ERK1/2 and Src, increased O2 ∙− production, and decreased A23187-induced NO production in ECs. Pretreatment of eMPs with apocynin diminished eMP-mediated effects on ROS and NO production but had no effect on eMP-mediated kinase activation or impairment in vasorelaxation. Our findings identify a novel mechanism whereby eMP-derived ROS contributes to MP bioactivity.These interactions may be important in conditions associated with vascular injury and increased eMP formation

Item Type:Articles
Additional Information:DB was supported by a fellowship from the Heart and Stroke Foundation of Canada/Pfizer Canada and a Kidney Research Scientist Core Education and National Training Program (KRESCENT) New Investigator Award. DB is funded by a grant from the Canadian Diabetes Association (OG-3-14-4548-DB). RMT is supported through a British Heart Foundation Chair (29762).
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Burger, D., Turner, M., Munkonda, M. N., and Touyz, R. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Oxidative Medicine and Cellular Longevity
Publisher:Hindawi Publishing Corporation
ISSN (Online):1942-0994
Copyright Holders:Copyright © 2016 Dylan Burger et al.
First Published:First published in Oxidative Medicine and Cellular Longevity 2016:5047954
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
607381Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)CH/12/4/29762RI CARDIOVASCULAR & MEDICAL SCIENCES