Submitted on March 1, 2007
Accepted on January 14, 2008
Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging
Helene Genevieve Bulckaen1*, Gaetan Prevost2, Eric Boulanger2, Geraldine Robitaille2, Valerie Roquet2, Cedric Gaxatte2, Guillaume Garcon3, Bruno Corman2, Pierre Gosset4, Pirouz Shirali3, Colette Creusy4, and Francois Puisieux2
1 Department of Internal Medicine and Geriatrics, Lille Catholic Institute Hospital, Lomme, France
2 Laboratory of Vascular Aging Biology, School of Medicine, University Hospital of Lille, Lille, France
3 Research Laboratory on Industrial and Environmental Toxicology, Industrial Environment Research Center, Littoral University, Dunkerque, France
4 Pathology Department, Lille Catholic Institute Hospital de Lille, Lomme, France
* To whom correspondence should be addressed. E-mail: Bulckaen.helene{at}ghicl.net.
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 (ACh) of phenylephrine (Phe)-induced precontracted aortic segments isolated from 12-, 36-, 60- and 84-week-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 (MDA) and 8-hydroxy-2’-deoxyguanosine (8-OhdG) was in addition quantified.
Compared to that of 12-week-old mice, the EDR was significantly reduced in 60- and 84-week-old mice (p<0.05). 68-week-old mice treated with aspirin displayed a higher EDR compared to 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 was observed. The protective effect of aspirin was not observed when treatment was initiated in older mice (96 weeks 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.
