Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging

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-dos...

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Bibliographic Details
Published in:	American journal of physiology. Heart and circulatory physiology Vol. 294; no. 4; p. H1562
Main Authors:	Bulckaen, Hélène, Prévost, Gaétan, Boulanger, Eric, Robitaille, Géraldine, Roquet, Valérie, Gaxatte, Cédric, Garçon, Guillaume, Corman, Bruno, Gosset, Pierre, Shirali, Pirouz, Creusy, Colette, Puisieux, François
Format:	Journal Article
Language:	English
Published:	United States 01-04-2008
Subjects:	Acetylcholine - pharmacology Age Factors Aging - metabolism Aging - pathology Animals Antioxidants - administration & dosage Aorta - drug effects Aorta - metabolism Aorta - physiopathology Aspirin - administration & dosage Cardiovascular Diseases - metabolism Cardiovascular Diseases - pathology Cardiovascular Diseases - physiopathology Cardiovascular Diseases - prevention & control Deoxyguanosine - analogs & derivatives Deoxyguanosine - metabolism Dose-Response Relationship, Drug Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Endothelium, Vascular - pathology Endothelium, Vascular - physiopathology Male Malondialdehyde - metabolism Mice Mice, Inbred C57BL Models, Animal Oxidative Stress - drug effects Phenylephrine - pharmacology Vasoconstrictor Agents - pharmacology Vasodilation - drug effects Vasodilator Agents - pharmacology
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Summary:	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.
ISSN:	0363-6135
DOI:	10.1152/ajpheart.00241.2007