[Antiatherosclerotic mechanism of aspirin: experiment with rabbits].
OBJECTIVE
To observe the effects of aspirin on nuclear factor kappaB (NF-kappaB)-DNA binding activity and on the expression of cyclooxygenase-2 (COX-2) in atherosclerotic plaque so as to explore its antiatherosclerotic mechanism.


METHODS
Thirty-six New Zealand male rabbits were randomly divided into 3 equal groups: high-cholesterol (HC) group, fed with food high in cholesterol and perfused into the empty stomach daily with distilled water for 12 weeks, high-cholesterol and aspirin (HC + A) group, fed with food high in cholesterol and perfused into the empty stomach daily with aspirin solution, and normal control (NC) group, fed with normal food and perfused into the empty stomach daily with distilled water, before the experiment, and 4, 8, and 12 weeks after the beginning of experiment peripheral blood samples were collected. The serum lipids were detected with enzymatic assays; and enzyme-linked immunosorbent assay was used to detect the level of high sensitive C-reactive protein (hs-CRP). By the end of experiment the rabbits were killed to take out the specimens of aorta to observe the neointima thickness and plaque area of aorta. Electrophoretic mobility shift assay was used to detect the NF-kappaB-DNA binding activity, and immunohistochemistry and morphometry were performed to observe the expression of COX-2 protein, the neointima thickness and plaque area of aorta respectively in all three groups.


RESULTS
The levels of serum lipids, hs-CRP, NF-kappaB-DNA binding activity, expression of COX-2 protein, and neointima thickness and plaque area of aorta in the HC and HC + A groups were all significantly higher than those in the NC group (P < 0.05 -0.01). There was no significant differences in the serum lipids between the HC and HC + A groups (all P > 0.05), however, the levels of hs-CRP, NF-kappaB-DNA binding activity, expression of COX-2 protein, and neointima thickness and plaque area of aorta of the HC + A group were (5.14 +/- 0.32) microg/ml, (14.6 +/- 2.7) microg/ml, (0.342 +/- 0.02)A, (165 +/- 24) microm, and (24.3 +/- 7.6)% respectively, all significantly lower than those of the HC group [(9.39 +/- 0.79) microg/ml, (32.4 +/- 4.7) microg/ml, (0.572 +/- 0.061) A, (337 +/- 64) microm, and (49.5 +/- 21.3)%, all P < 0.05). By reducing the expression of COX-2.
Yang
Xiao-Yun
XY
Department of Cardiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Wang
Lin
L
Zhou
Ning
N
Zeng
He-Song
HS
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008055:Lipids / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011817:Rabbits; D011897:Random Allocation; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D002791:Cholesterol, Dietary; D016861:Cyclooxygenase Inhibitors; D008055:Lipids; D016328:NF-kappa B; D002097:C-Reactive Protein; D004247:DNA; D051546:Cyclooxygenase 2; D001241:Aspirin