The continuous administration of aspirin attenuates atherosclerosis in apolipoprotein E-deficient mice

Aspirin reduces the incidence of thrombotic occlusive events. Classically t his has been thought to be due to the platelet inhibitory action of aspirin but it has recently been shown that inflammation plays a predominant role in the initiation and progression of lesions in atherosclerosis. In humans, treatment with aspirin reduces cardiovascular risk and slows carotid plaqu e growth in a dose-dependent fashion. rme have explored this issue in Apo E -deficient mice on a high-fat, high cholesterol diet which provided these a nimals with a continuous administration of 500 mug/day of acetylsalicylic a cid in the drinking water. After 10 weeks of treatment, the size of the ath erosclerotic lesion at the aortic sinus had reduced by 35%. At the end of t he trial there were no significant changes in either plasma lipids or in th e quantitative distribution among lipoproteins. Likewise, the total antioxi dant status and the resistance of plasma to oxidation in vitro was similar and there was no change in the distribution of iron de posits and in the re lative composition of plasma pro-oxidants and antioxidants, or in the conce ntration of plasma in ferritin. Therefore, it is our hypothesis that the an tiinflammatory effect is responsible for the reduction in lesion size. We p ropose that antiinflammatory molecules which do not cause gastrointestinal complications should be tested in humans to determine long-term efficacy in the attenuation of atherosclerosis. (C) 2000 Elsevier Science Inc. All rig hts reserved.