Peroxisome proliferator-activated receptor-γ protects against vascular aging. Am J Physiol Regul Integr Comp Physiol 2012 May 15;302(10):R1184-90
Date
03/31/2012Pubmed ID
22461176Pubmed Central ID
PMC3362146DOI
10.1152/ajpregu.00557.2011Scopus ID
2-s2.0-84861158340 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
Vascular disease occurs commonly during aging. Carotid artery and cerebrovascular disease are major causes of stroke and contributors to dementia. Recent evidence suggests that peroxisome proliferator-activated receptor-γ (PPARγ) may play a protective role in the vasculature, but the potential importance of PPARγ in vascular aging is unknown. To examine the hypothesis that PPARγ normally protects against vascular aging, we studied heterozygous knockin mice expressing a human dominant-negative mutation in PPARγ (P465L, designated L/+). Endothelial dysfunction, a major contributor to vascular disease, was studied using carotid arteries from adult (8 ± 1 mo) and old (24 ± 1 mo) L/+ mice and wild-type littermates. In arteries from wild-type mice, responses to the endothelium-dependent agonist ACh were similar in adult and old wild-type mice but were reduced by ∼50% in old L/+ mice (n = 7-10, P < 0.05). Impaired responses in arteries from old L/+ mice were restored to normal by a scavenger of superoxide. Relaxation of arteries to nitroprusside (an NO donor) was similar in all groups. Contraction of arteries to U46619 was not affected by age or genotype, while maximal responses to endothelin-1 were reduced with age in both wild-type and L/+ mice. Vascular expression (mRNA) of the catalytic component of NADPH oxidase (Nox2) was not altered in wild-type mice but was increased significantly in old L/+ mice. These findings provide the first evidence that interference with PPARγ function accelerates vascular aging, suggesting a novel role for PPARγ in protecting against age-induced oxidative stress and endothelial dysfunction.
Author List
Modrick ML, Kinzenbaw DA, Chu Y, Sigmund CD, Faraci FMAuthor
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic AcidAging
Animals
Aorta
Carotid Arteries
Endothelium, Vascular
Female
Gene Knock-In Techniques
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Models, Animal
Nitroprusside
Oxidative Stress
PPAR gamma
Vasoconstrictor Agents
Vasodilator Agents
