Endothelial microparticles prevent lipid‐induced endothelial damage via Akt/eNOS signaling and reduced oxidative stress

• Published in: The FASEB journal Vol. 31; no. 10; pp. 4636 - 4648
• Main Authors: Mahmoud, Ayman M., Wilkinson, Fiona L., McCarthy, Eoghan M., Moreno‐Martinez, Daniel M., Langford‐Smith, Alexander, Romero, Miguel, Duarte, Juan, Alexander, M. Yvonne
• Format: Journal Article
• Language: English
• Published: United States Federation of American Societies for Experimental Biology 01.10.2017
• Subjects: Cell-Derived Microparticles - metabolism; Endothelial Cells - metabolism; endothelial dysfunction; Endothelium, Vascular - metabolism; extracellular microvesicles; Humans; Lipids - pharmacology; NADPH Oxidases - metabolism; Nitric Oxide Synthase Type III - metabolism; Nrf2; Oncogene Protein v-akt - metabolism; Oxidative Stress - physiology; Reactive Oxygen Species - metabolism; Vasodilation - drug effects; Nrf2; endothelial dysfunction; extracellular microvesicles
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.201601244RR

ABSTRACT Endothelial microparticles (EMPs) are endothelium‐derived submicron vesicles that are released in response to diverse stimuli and are elevated in cardiovascular disease, which is correlated with risk factors. This study investigates the effect of EMPs on endothelial cell function and dysfunction in a model of free fatty acid (FFA) palmitate‐induced oxidative stress. EMPs were generated from TNF‐α‐stimulated HUVECs and quantified by using flow cytometry. HUVECs were treated with and without palmitate in the presence or absence of EMPs. EMPs were found to carry functional eNOS and to protect against oxidative stress by positively regulating eNOS/Akt signaling, which restored NO production, increased superoxide dismutase and catalase, and suppressed NADPH oxidase and reactive oxygen species (ROS) production, with the involvement of NF‐erythroid 2‐related factor 2 and heme oxygenase‐1. Conversely, under normal conditions, EMPs reduced NO release and increased ROS and redox‐sensitive marker expression. In addition, functional assays using EMP‐treated mouse aortic rings that were performed under homeostatic conditions demonstrated a decline in endothelium‐dependent vasodilatation, but restored the functional response under lipid‐induced oxidative stress. These data indicate that EMPs harbor functional eNOS and potentially play a role in the feedback loop of damage and repair during homeostasis, but are also effective in protecting against FFA‐induced oxidative stress; thus, EMP function is reflected by the microenvironment.— Mahmoud, A. M., Wilkinson, F. L., McCarthy, E. M., Moreno‐Martinez, D., Langford‐Smith, A., Romero, M., Duarte, J., Alexander, M. Y. Endothelial microparticles prevent lipid‐induced endothelial damage via Akt/eNOS signaling and reduced oxidative stress. FASEB J. 31, 4636–4648 (2017). www.fasebj.org