Stabilization of advanced atherosclerosis in low-density lipoprotein receptor-deficient mice by aspirin.
COX-1-dependent eicosanoid formation accelerates atherogenesis, and low-dose aspirin reduces early atherosclerosis. However, the role of aspirin in modulating progression of vascular atherosclerotic lesions once established is less investigated. We wished to determine the effect of low-dose aspirin on vascular inflammation, plaque composition, and progression of established atherosclerosis. Low-density lipoprotein receptor-deficient mice (LDLR(-/-)) were fed a high-fat diet for 3 months. At this time, one group of mice underwent baseline analysis. Two additional groups, while continuing the high-fat diet, were randomized to receive placebo or aspirin for additional 3 months. At the end of the study, LDLR(-/-) mice that had received aspirin had suppressed biosynthesis of thromboxane B2, the major products of COX-1 activity, reduced monocyte chemoattractant protein-1, and soluble intercellular adhesion molecule-1 levels compared with controls. Compared with baseline, the placebo group had significant progression of atherosclerosis. In contrast, aspirin treated mice showed a significant reduction in progression of atherosclerosis, and a significant decrease in foam cell content. These results suggest that in murine atherosclerosis, low-dose aspirin retards progression of established and advanced vascular atherosclerotic lesions by suppressing the formation of bioactive lipids and vascular inflammation.
Cyrus
Tillmann
T
Division of Cardiology, Department of Medicine, Barnes-Jewish Hospital, Washington University School of Medicine, Saint Louis, MO 63110, USA. tcyrus@im.wustl.edu
Yao
Yuemang
Y
Tung
Liun X
LX
Praticò
Domenico
D
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D051545:Cyclooxygenase 1 / Q000097:blood / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D011973:Receptors, LDL / Q000097:blood / Q000172:deficiency*; D013929:Thromboxane B2 / Q000097:blood; D016896:Treatment Outcome
D016861:Cyclooxygenase Inhibitors; D011973:Receptors, LDL; D013929:Thromboxane B2; D051545:Cyclooxygenase 1; D001241:Aspirin