Effects of simvastatin on NF-kappaB-DNA binding activity and monocyte chemoattractant protein-1 expression in a rabbit model of atherosclerosis.
To observe the effects of simvastatin on nuclear factor kappaB (NF-kappaB)-DNA binding activity and on the expression of monocyte chemoattractant protein-1 (MCP-1) in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group (LC), high-cholesterol group (HC), high-cholesterol+simvastatin group (HC+S) and then were fed for 12 weeks. At the end of the experiment, standard enzymatic assays, electrophoretic mobility shiftassay (EMSA), immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-kappaB-DNA binding activity, MCP-1 protein expression, intima thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-kappaB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC+S groups were significantly lower than those in the HC group (P<0.05). There was no significant difference in the serum lipids between the LC and HC+S groups (P>0.05), but the NF-kappaB-DNA binding activity, the expression of MCP-1 protein and the intima thickness and plaque area of aorta in the HC+S group were significantly decreased as compared to the LC group (P<0.05). This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NF-kappaB-DNA binding activity and by reducing the expression of MCP-1 protein.
Yang
Xiaoyun
X
Department of Cardiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Wang
Lin
L
Zeng
Hesong
H
Dubey
Laxman
L
Zhou
Ning
N
Pu
Jun
J
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018932:Chemokine CCL2 / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011817:Rabbits; D011897:Random Allocation; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use
D018932:Chemokine CCL2; D004268:DNA-Binding Proteins; D000960:Hypolipidemic Agents; D016328:NF-kappa B; D002784:Cholesterol; D019821:Simvastatin