title: Age-related differences in the effects of α and γ peroxisome proliferator-activated receptor subtype agonists on endothelial vasodilation in human microvessels.
abstract: Endothelial vasodilation in human vessels is impaired by aging and other cardiovascular risk factors (CVRF) but the differential impact of aging and CVRF in human endothelial function is not completely elucidated. The aim of this work was to evaluate the influence of aging on the effects of peroxisome proliferator-activated receptor (PPAR)-α and -γ subtype agonists on endothelium-dependent vasodilation of isolated human vessels from subjects with or without CVRF. Human mesenteric microarteries were dissected from omentum specimens obtained from subjects younger or older than 60 years having or not CVRF and mounted in wire myographs to evaluate endothelium-dependent relaxation to bradykinin (BK). Aging and CVRF independently reduced endothelium-dependent relaxations. An additional impairment was produced when aging and CVRF co-existed (p<0.001). In vessels from adult subjects PPARγ agonist, GW1929 (1 μM) improved BK-induced responses only in those obtained from subjects with CVRF. By contrast, GW1929 improved the responses in vessels from elderly subjects having or not CVRF. PPARα agonist, GW7647 (1 μM), enhanced endothelial vasodilation in adults with CVRF (p<0.001) but lack any effect in vessels from older subjects having or not CVRF. In vessels from subjects with CVRF, superoxide dismutase (SOD; 100 U/ml) improved BK-induced responses only in elderly subjects (p<0.001). Vascular aging negatively impacts endothelial function independently of the presence of additional CVRF through specific molecular mechanisms involving superoxide generation. While PPARγ activation remains effective, the improving effects of PPARα agonists on endothelial responses disappear in aged human vessels.
authors: Instituto Ramón y Cajal de Investigación Sanitaria, Madrid-28034, Spain.
authors: Javier
authors: J
authors: Angulo
authors: Susana
authors: S
authors: Vallejo
authors: Mariam
authors: M
authors: El Assar
authors: Javier
authors: J
authors: García-Septiem
authors: Carlos F
authors: CF
authors: Sánchez-Ferrer
authors: Leocadio
authors: L
authors: Rodríguez-Mañas
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001577:Benzophenones / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D055806:Microvessels / Q000187:drug effects*; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D047493:PPAR alpha / Q000037:antagonists & inhibitors*; D047495:PPAR gamma / Q000037:antagonists & inhibitors*; D010671:Phenylurea Compounds / Q000494:pharmacology; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D001577:Benzophenones; D002087:Butyrates; D016166:Free Radical Scavengers; C453899:GW 7647; D047493:PPAR alpha; D047495:PPAR gamma; D010671:Phenylurea Compounds; D013481:Superoxides; D014443:Tyrosine; D013482:Superoxide Dismutase; C120099:GW 1929