The effect of the long term aspirin administration on the progress of atherosclerosis in apoE-/- LDLR-/- double knockout mouse
Received 26 March 2009; received in revised form 14 October 2009; accepted 9 November 2009.
Abstract
We have investigated the effects of differential aspirin doses on atherogenesis. Aspirin was given to homozygous, apoE-/- and LDLR-/- double deficient mice for 12weeks. The development of arteriosclerosis was determined morphologically by image analysis and endothelial cell function was assessed by measurement of peripheral nitric oxide (NO).
Methods
ApoE-/- LDLR-/-double knockout mice were bred and maintained with a high fat diet containing aspirin (4 and 40mg/kg B.W. /day) for twelve weeks. The development of arteriosclerosis was monitored by estimating the total area of atherosclerotic lesions in the entire aorta. Acetylcholine-induced NO release was measured in vivo using electrochemical sensors. The expression of eNOS on the endothelial surface was determined by immuno-staining. Plasma prostaglandin F1α (PGF1α), serum thromboxian B2 (TXB2) and total cholesterol were measured using enzymatic assay. Bleeding time was measured by tail cut method.
Results
Arteriosclerosis in the 4mg/kg/day aspirin group was decreased significantly compared with the placebo group, but not in the 40mg/kg/day aspirin group. Acetylcholine-induced NO release was significantly depressed in the 40mg/kg/day aspirin group. Immunochemical analysis with anti-eNOS antibody supported these findings. In the 4mg/kg/day aspirin group, the severe suppression of PGI2 production was not confirmed in spite of decreasing TXB2 production, but not in the 40mg/kg/day aspirin group.
Conclusion
Our results suggest that endothelial dysfunction with low dose aspirin improved, reduced progression of atherosclerosis in apoE-/- and LDLR-/- double deficient mice and provides a pathophysiological basis for the beneficial effects of aspirin in atherosclerosis, and low doses appeared to be more efficient than high doses.
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