Open AccessInterleukin‐10 protects against aging‐induced endothelial dysfunction
Author(s) -
Kinzenbaw Dale A.,
Chu Yi,
Peña Silva Ricardo A.,
Didion Sean P.,
Faraci Frank M.
Publication year - 2013
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.1002/phy2.149
Subject(s) - endothelial dysfunction , nadph oxidase , medicine , proinflammatory cytokine , endocrinology , acetylcholine , superoxide , oxidative stress , endothelium , vasodilation , inflammation , cytokine , chemistry , biochemistry , enzyme
Abstract Carotid and cerebrovascular disease increase markedly with age contributing to stroke and cognitive impairment. Inflammation is a key element of vascular disease. In these studies, we tested the hypothesis that interleukin‐10 ( IL ‐10), a potent anti‐inflammatory cytokine, protects against aging‐induced endothelial dysfunction. Responses of carotid arteries from adult (5 ± 1 months) and old (22 ± 1 months) wild‐type and IL ‐10‐deficient mice were examined in vitro. Acetylcholine (an endothelium‐dependent agonist) produced relaxation in arteries from adult wild‐type that was not altered in old mice. In contrast, relaxation to acetylcholine in arteries from old IL ‐10‐deficient mice was reduced by ~50% ( P < 0.05). Tempol, a scavenger of superoxide, did not affect responses in adult or old wild‐type mice, but restored vasodilation to acetylcholine to normal in old IL ‐10‐deficient mice. Responses of the carotid artery to nitroprusside (an endothelium‐independent agonist) were not altered in any group. Vascular expression of IL ‐6 (a proinflammatory mediator of vascular disease) and components of NADPH oxidase (a major source of superoxide) was increased in old IL ‐10‐deficient mice compared with wild‐type ( P < 0.05). These findings provide the first evidence that age‐related and superoxide‐mediated endothelial dysfunction occurs earlier with IL ‐10 deficiency. Our findings suggest a novel role for IL ‐10 to protect against age‐related increases in expression of IL ‐6, oxidative stress, and endothelial dysfunction.