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Effects of simvastatin on NF-κB-DNA binding activity and monocyte chemoattractant protein-1 expression in a rabbit model of atherosclerosis

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Summary

To observe the effects of simvastatin on nuclear factor kappaB (NF-κB)-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 shift assay (EMSA), immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-κB-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-κB-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-κB-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-κB-DNA binding activity and by reducing the expression of MCP-1 protein.

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References

  1. Menno P J de Winther, Edwin K, Georg Ket al. Nuclear factor κB signaling in atherogenesis. Arterioscler Thromb Vasc Biol, 2005, 25: 904–914

    Article  Google Scholar 

  2. Robert K, Hans M G P, Jef J Eet al. Rosuvastatin reduces atherosclerosis development beyond and independent of its plasma cholesterol-lowering effect in APOE* 3-Leiden transgenic mice. Circulation, 2003, 108: 1368–1374

    Article  Google Scholar 

  3. Pu J, Wang L, Zhang C Tet al. Defibrase inhibits atherosclerosis induced by immunologic injury and high-fat diet in rabbit through restoring nitric oxide availability. Arterioscler Thromb Vasc Biol, 2004, 24: E7-E10

    Article  Google Scholar 

  4. Dwarakanath R S, Sahar S, Reddy M Aet al. Regulation of monocyte chemoattractant protein-1 by the oxidized lipid, 13-hydroperoxyoctadecadienoic acid, in vascular smooth muscle cells via nuclear factor-kappa B (NF-kappa B). J Mol Cell Cardiol, 2004, 36(4): 585–595

    Article  PubMed  CAS  Google Scholar 

  5. Claudia M, Evangelos A, Serafim Ket al. Canonical pathway of nuclear factor κB activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis. PNAS, 2004, 15(101): 5634–5639

    Google Scholar 

  6. Brand K, Page S, Rogler Get al. Activated Transcription factor nuclear factor-kappa B is pregant in the athcrosclerotic lesion. J Clin Invest, 1996, 97: 1715–1722

    Article  PubMed  CAS  Google Scholar 

  7. James X R, Joan W B, Mark B Tet al. Lysophosphatidylcholine stimulates monocyte chemoattractant protein-1 gene expression in rat aortic smooth muscle cells. Arterioscler Thromb Vasc Biol, 2002, 22: 1617–1623

    Article  Google Scholar 

  8. Ikeda U, Matsui K, Murakami Yet al. Monocyte chemoattractant protein-1 and coronary artery discase. Clin Cardiol, 2002, 25: 143–147

    Article  PubMed  Google Scholar 

  9. Jacob G, Arnon A, Pnina Ket al. Functional inhibition of Ras by S-trans, trans-farnesyl thiosalicylic acid attenuates atherosclerosis in apolipoprotein E knockout mice. Circulation, 2002, 105: 2416–2422

    Article  Google Scholar 

  10. Ortego M, Gomez-Hernandez A, Vidal Cet al. HMG-CoA reductase inhibitors reduce I kappa B kinase activity induced by oxidative stress in monocytes and vascular smooth muscle cells. J Cardiovasc Pharmacol, 2005, 45(5): 468–475

    Article  PubMed  Google Scholar 

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YANG Xiaoyun, female, born in 1966, M. D., Ph. D.

This project was supported by a grant from the National Natural Sciences Foundation of China (No. 30470713).

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Xiaoyun, Y., Lin, W., Hesong, Z. et al. Effects of simvastatin on NF-κB-DNA binding activity and monocyte chemoattractant protein-1 expression in a rabbit model of atherosclerosis. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 26, 194–198 (2006). https://doi.org/10.1007/BF02895814

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  • DOI: https://doi.org/10.1007/BF02895814

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