title: Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging.
abstract: The age-related impairment of endothelium-dependent vasodilatation contributes to increased cardiovascular risk in the elderly. For primary and secondary prevention, aspirin can reduce the incidence of cardiovascular events in this patient population. The present work evaluated the effect of low-dose aspirin on age-related endothelial dysfunction in C57B/J6 aging mice and investigated its protective antioxidative effect. Age-related endothelial dysfunction was assessed by the response to acetylcholine of phenylephrine-induced precontracted aortic segments isolated from 12-, 36-, 60-, and 84-wk-old mice. The effect of low-dose aspirin was examined in mice presenting a decrease in endothelial-dependent relaxation (EDR). The effects of age and aspirin treatment on structural changes were determined in mouse aortic sections. The effect of aspirin on the oxidative stress markers malondialdehyde and 8-hydroxy-2'-deoxyguanosine (8-OhdG) was also quantified. Compared with that of 12-wk-old mice, the EDR was significantly reduced in 60- and 84-wk-old mice (P < 0.05); 68-wk-old mice treated with aspirin displayed a higher EDR compared with control mice of the same age (83.9 +/- 4 vs. 66.3 +/- 5%; P < 0.05). Aspirin treatment decreased 8-OHdG levels (P < 0.05), but no significant effect on intima/media thickness ratio was observed. The protective effect of aspirin was not observed when treatment was initiated in older mice (96 wk of age). It was found that low-dose aspirin is able to prevent age-related endothelial dysfunction in aging mice. However, the absence of this effect in the older age groups demonstrates that treatment should be initiated early on. The underlying mechanism may involve the protective effect of aspirin against oxidative stress.
authors.affiliation: Dept. of Internal Medicine and Geriatrics, Lille Catholic Institute Hospital, 59160 Lomme, France. Bulckaen.Helene@ghicl.net
authors.forename: Hélène
authors.initials: H
authors.lastname: Bulckaen
authors.forename: Gaétan
authors.initials: G
authors.lastname: Prévost
authors.forename: Eric
authors.initials: E
authors.lastname: Boulanger
authors.forename: Géraldine
authors.initials: G
authors.lastname: Robitaille
authors.forename: Valérie
authors.initials: V
authors.lastname: Roquet
authors.forename: Cédric
authors.initials: C
authors.lastname: Gaxatte
authors.forename: Guillaume
authors.initials: G
authors.lastname: Garçon
authors.forename: Bruno
authors.initials: B
authors.lastname: Corman
authors.forename: Pierre
authors.initials: P
authors.lastname: Gosset
authors.forename: Pirouz
authors.initials: P
authors.lastname: Shirali
authors.forename: Colette
authors.initials: C
authors.lastname: Creusy
authors.forename: François
authors.initials: F
authors.lastname: Puisieux
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000109:Acetylcholine / Q000494:pharmacology; D000367:Age Factors; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001241:Aspirin / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D000109:Acetylcholine; D001241:Aspirin