The effect of the long term aspirin administration on the progress of atherosclerosis in apoE-/- LDLR-/- double knockout mouse.

Abstract

UNLABELLED:

We have investigated the effects of differential aspirin doses on atherogenesis. Aspirin was given to homozygous, apoE(-/-) and LDLR(-/-) double deficient mice for 12 weeks. 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 40 mg/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 F1alpha (PGF(1 alpha)), serum thromboxian B(2) (TXB(2)) and total cholesterol were measured using enzymatic assay. Bleeding time was measured by tail cut method.

RESULTS:

Arteriosclerosis in the 4 mg/kg/day aspirin group was decreased significantly compared with the placebo group, but not in the 40 mg/kg/day aspirin group. Acetylcholine-induced NO release was significantly depressed in the 40 mg/kg/day aspirin group. Immunochemical analysis with anti-eNOS antibody supported these findings. In the 4 mg/kg/day aspirin group, the severe suppression of PGI(2) production was not confirmed in spite of decreasing TXB(2) production, but not in the 40 mg/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.

• Authors: Y Yamamoto, T Yamashita, F Kitagawa, K Sakamoto, J C Giddings, J Yamamoto
• Journal: Thrombosis research (Thromb Res) Vol. 125 Issue 3 Pg. 246-52 (Mar 2010) ISSN: 1879-2472 [Electronic] United States
• PMID: 20005558 (Publication Type: Journal Article)
• Copyright: (c) 2009 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Apolipoproteins E
• Nitric Oxide
• Nitric Oxide Synthase Type III
• Nos3 protein, mouse
• Acetylcholine
• Aspirin

Topics

• Acetylcholine (pharmacology)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Aorta (pathology)
• Apolipoproteins E (deficiency)
• Aspirin (pharmacology)
• Atherosclerosis (pathology)
• Diet, Atherogenic
• Dose-Response Relationship, Drug
• Endothelial Cells (metabolism)
• Endothelium, Vascular (metabolism)
• Homozygote
• Immunohistochemistry
• Male
• Mice
• Mice, Knockout
• Nitric Oxide (analysis, metabolism)
• Nitric Oxide Synthase Type III (analysis, metabolism)
• Time Factors