Effect of pioglitazone combined with simvastatin on the CD40-CD40 ligand system in rabbits with atherosclerosis

L. Xue, X.-H. 0zhu, X.-F. Yang, X.-C. Bao, X.-Q. Gao, Y.-H. Qiu, Z. Wu , X.-P. Ji, H.-W. Li

Department of Cardiovascular Medicine, The Third Affiliated Hospital of Liaoning Medical College, Jinzhou, Liaoning Province, China. xlxqcn@126.com

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• Metabolism

OBJECTIVE: This paper aims to investigate the interaction mechanism between pioglitazone/simvastatin and the CD40-CD40 ligand (CD40-CD40L) system and to determine their interaction effects on atherosclerosis in rabbits.

MATERIALS AND METHODS: Forty rabbits were randomly divided into five groups of eight: normal control, hyperlipidemia model, pioglitazone, simvastatin, and pioglitazone combined with simvastatin therapy. The rabbits were raised for 16 weeks. Blood samples and the aortic length were taken after 16 weeks with the following indicators: (1) blood lipid measurement [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] were measured; (2) measurement of serum high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble CD40 ligand (sCD40L), and matrix metallopeptidase-9 (MMP-9) by enzyme-linked immunosorbent assay; (3) aortic pathological observation and measurement of the area ratios for plaque/intimal; and (4) expression determination of CD40L in plaque parts by immunohistochemistry.

RESULTS: In the treatment groups, the levels of TC, TG, LDL-C, hsCRP, sVCAM-1, sICAM-1, sCD40L, and MMP-9 increased, and HDL-C level, plaque/intimal area ratio, and CD40 expression in the plaque parts decreased. Improved effects were also found in the combination treatment group.

CONCLUSIONS: Pioglitazone and simvastatin may inhibit different functions, such as inflammatory response and lipid regulation, by inhibiting the CD40-CD40L signaling pathway to suppress the formation of atherosclerosis. Therefore, the combined application of pioglitazone and simvastatin has synergistic effects.

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