Peroxisome proliferator-activated receptor-Î³ protects against vascular aging

Mary L Modrick; Dale A Kinzenbaw; Yi Chu; Curt D Sigmund; Frank M Faraci

doi:10.1152/ajpregu.00557.2011

Back

Peroxisome proliferator-activated receptor-Î³ protects against vascular aging

Journal article

Open access

Peer reviewed

Peroxisome proliferator-activated receptor-Î³ protects against vascular aging

Mary L Modrick, Dale A Kinzenbaw, Yi Chu, Curt D Sigmund and Frank M Faraci

American journal of physiology. Regulatory, integrative and comparative physiology, Vol.302(10), pp.R1184-R1190

05/15/2012

DOI: 10.1152/ajpregu.00557.2011

PMCID: PMC3362146

PMID: 22461176

Files and links (1)

url

https://doi.org/10.1152/ajpregu.00557.2011View

Published (Version of record) Open Access

Abstract

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.

endothelium

nitric oxide

cardiovascular risk factors

Cardiovascular and Renal Integration

oxidative stress

Details

Title: Subtitle: Peroxisome proliferator-activated receptor-Î³ protects against vascular aging
Creators: Mary L Modrick - Departments of
Dale A Kinzenbaw - Departments of
Yi Chu - Departments of
Curt D Sigmund - Pharmacology, Cardiovascular Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa
Frank M Faraci - Departments of
Resource Type: Journal article
Publication Details: American journal of physiology. Regulatory, integrative and comparative physiology, Vol.302(10), pp.R1184-R1190
DOI: 10.1152/ajpregu.00557.2011
PMID: 22461176
PMCID: PMC3362146
NLM abbreviation: Am J Physiol Regul Integr Comp Physiol
ISSN: 0363-6119
eISSN: 1522-1490
Publisher: American Physiological Society; Bethesda, MD
Grant note: HL-38901; HL-62984; HL84207; HL61446; NS-24621 / National Institutes of Health
Language: English
Date published: 05/15/2012
Academic Unit: Molecular Physiology and Biophysics; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040596602771

Metrics

15 Record Views

21 Times Cited - Web of Science