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The continuous administration of aspirin attenuates atherosclerosis in apolipoprotein E-deficient mice
1Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan de Reus, Spain.
Insights
Aspirin, or acetylsalicylic acid, significantly reduced atherosclerotic lesion size in mice by 35%. This study suggests aspirin
Area of Science:
- Cardiovascular Research
- Pharmacology
- Immunology
Background:
- Atherosclerosis is initiated and progressed by inflammation.
- Aspirin (acetylsalicylic acid) is known to reduce thrombotic events.
- Previous studies suggest aspirin's anti-inflammatory properties may impact cardiovascular risk.
Purpose of the Study:
- To investigate the effect of aspirin on atherosclerotic lesion size in Apo E-deficient mice.
- To explore the role of anti-inflammatory mechanisms in aspirin's cardiovascular protective effects.
Main Methods:
- Apo E-deficient mice were fed a high-fat, high-cholesterol diet.
- Mice received continuous administration of acetylsalicylic acid (500 microg/day) in drinking water for 10 weeks.
- Atherosclerotic lesion size at the aortic sinus was measured.
- Plasma lipids, antioxidant status, and iron deposits were analyzed.
Main Results:
- Acetylsalicylic acid treatment reduced atherosclerotic lesion size by 35% at the aortic sinus.
- No significant changes were observed in plasma lipids, lipoproteins, or antioxidant status.
- Iron deposits and plasma pro-oxidant/antioxidant composition remained unchanged.
Conclusions:
- The anti-inflammatory effect of aspirin is hypothesized to be responsible for the reduction in lesion size.
- Further research into non-gastrointestinal irritating anti-inflammatory agents is warranted for atherosclerosis treatment.
Abstract:
Aspirin reduces the incidence of thrombotic occlusive events. Classically this 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 plaque growth in a dose-dependent fashion. We have explored this issue in Apo E-deficient mice on a high-fat, high cholesterol diet which provided these animals with a continuous administration of 500 microg/day of acetylsalicylic acid in the drinking water. After 10 weeks of treatment, the size of the atherosclerotic lesion at the aortic sinus had reduced by 35%. At the end of the trial there were no significant changes in either plasma lipids or in the quantitative distribution among lipoproteins. Likewise, the total antioxidant status and the resistance of plasma to oxidation in vitro was similar and there was no change in the distribution of iron deposits and in the relative composition of plasma pro-oxidants and antioxidants, or in the concentration of plasma in ferritin. Therefore, it is our hypothesis that the antiinflammatory effect is responsible for the reduction in lesion size. We propose that antiinflammatory molecules which do not cause gastrointestinal complications should be tested in humans to determine long-term efficacy in the attenuation of atherosclerosis.