Aging-associated metabolic disorder induces Nox2 activation and oxidative damage of endothelial function

Free Radical Biology & Medicine
Lampson M FanJian-Mei Li

Abstract

Oxidative stress attributable to the activation of a Nox2-containing NADPH oxidase is involved in the development of vascular diseases and in aging. However, the mechanism of Nox2 activation in normal aging remains unclear. In this study, we used age-matched wild-type (WT) and Nox2 knockout (KO) mice at 3-4 months (young); 11-12 months (middle-aged) and 21-22 months (aging) to investigate age-related metabolic disorders, Nox2 activation and endothelial dysfunction. Compared to young mice, middle-aged and aging WT mice had significant hyperglycaemia, hyperinsulinaemia, increased systemic oxidative stress and higher blood pressure. Endothelium-dependent vessel relaxation to acetylcholine was significantly impaired in WT aging aortas, and this was accompanied by increased Nox2 and ICAM-1 expressions, MAPK activation and decreased insulin receptor expression and signaling. However, these aging-associated disorders were significantly reduced or absent in Nox2KO aging mice. The effect of metabolic disorder on Nox2 activation and endothelial dysfunction was further confirmed using high-fat diet-induced obesity and insulin resistance in middle-aged WT mice treated with apocynin (a Nox2 inhibitor). In vitro experiments showed that in re...Continue Reading

Citations

Aug 19, 2017·Antioxidants & Redox Signaling·Arash Haghikia, Ulf Landmesser
Jun 21, 2018·Basic & Clinical Pharmacology & Toxicology·Xin LiMing Xu
Jul 22, 2019·Experimental Physiology·Daniel W Trott, Paul J Fadel
Mar 21, 2018·Frontiers in Cardiovascular Medicine·Goro KatsuumiTohru Minamino
Apr 26, 2020·Cells·Ann Marie CentnerGloria Salazar
Jun 3, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Mingjun ShiMing Chang Hu
Jul 23, 2019·The Journal of Clinical Investigation·Lampson M FanJian-Mei Li
Jun 18, 2019·Oxidative Medicine and Cellular Longevity·Chirayu D PandyaSadanand Fulzele
May 2, 2018·International Journal of Molecular Sciences·Gloria Salazar
Jan 25, 2020·Oxidative Medicine and Cellular Longevity·Adrian GerickeVerena Prokosch
May 1, 2021·Antioxidants·Filip Kolodziej, Ken D O'Halloran

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
fluorescence microscopy
light microscopy

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