Vascular inflammation in aging: role of increased mitochondrial H2O2 production in endothelial NF‐kB activation

Abstract

Aging elicits vascular oxidative stress and a pro‐inflammatory shift in endothelial gene expression profile. To elucidate the link between increased oxidative stress and vascular inflammation in aging the carotid arteries and aortas of young and aged (24 mo) F344 rats were compared. In aged vessels there was an increased NF‐kB activity (assessed by luciferase reporter gene assay and NF‐kB binding assay), which was attenuated by scavenging H2O2. Aging did not alter the vascular expression of p65 and p50 subunits of NF‐kB. In endothelial cells of aged vessels there was an increased production of H2O2, which was attenuated by the mitochondrial uncoupler FCCP. In young arteries and cultured endothelial cells antimycin A plus succinate significantly increased mitochondrial H2O2 generation, which was associated with activation of NF‐kB. In aged vessels inhibition of NF‐kB (by PDTC, resveratrol) significantly attenuated inflammatory gene expression and inhibited monocyte adhesiveness. Thus, increased mitochondrial oxidative stress contributes to endothelial NF‐kB activation, which contributes to the pro‐inflammatory phenotypic alterations in the aged vasculature.