title: Interleukin-10 protects against aging-induced endothelial dysfunction.
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.
authors.affiliation: Department of Internal Medicine, Cardiovascular Center, Carver College of Medicine, University of Iowa Iowa City, 52242, Iowa.
authors.forename: Dale A
authors.initials: DA
authors.lastname: Kinzenbaw
authors.affiliation: Department of Internal Medicine, Cardiovascular Center, Carver College of Medicine, University of Iowa Iowa City, 52242, Iowa.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Internal Medicine, Cardiovascular Center, Carver College of Medicine, University of Iowa Iowa City, 52242, Iowa.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Peña Silva
authors.affiliation: Department of Internal Medicine, Cardiovascular Center, Carver College of Medicine, University of Iowa Iowa City, 52242, Iowa ; Department of Pharmacology, University of Mississippi Medical Center Jackson, 39216, Mississippi.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Didion
authors.affiliation: Department of Internal Medicine, Cardiovascular Center, Carver College of Medicine, University of Iowa Iowa City, 52242, Iowa ; Department of Pharmacology, Cardiovascular Center, Carver College of Medicine, University of Iowa Iowa City, 52242, Iowa.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Faraci
keywords: Endothelium; NADPH oxidase; interleukin-6; nitric oxide; oxidative stress