title: Synergistic effects of atorvastatin and rosiglitazone on endothelium protection in rats with dyslipidemia.
abstract: BACKGROUND
  Endothelial dysfunction is implicated in the initiation and progression of atherosclerosis. Whether atorvastatin combined with rosiglitazone has synergistic effects on endothelial function improvement in the setting of dyslipidemia is unknown.
  
  
  METHODS
  Dyslipidemia rat model was produced with high-fat and high-cholesterol diet administration. Thereafter, atorvastatin, rosiglitazone or atorvastatin combined with rosiglitazone were prescribed for 2 weeks. At baseline, 6 weeks of dyslipidemia model production, and 2 weeks of medical intervention, fasting blood was drawn for parameters of interest evaluation. At the end, myocardium was used for 15-deoxy-delta-12,14-PGJ2 (15-d-PGJ2) assessment.
  
  
  RESULTS
  Initially, there was no significant difference of parameters between sham and dyslipidemia groups. With 6 weeks' high-fat and high-cholesterol diet administration, as compared to sham group, serum levels of triglyceride (TG), total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) were significantly increased. Additionally, nitric oxide (NO) production was reduced and serum levels of malondialdehyde (MDA), C-reactive protein (CRP) and asymmetric dimethylarginine (ADMA) were profoundly elevated in dyslipidemia group. After 2 weeks' medical intervention, lipid profile was slightly improved in atorvastatin and combined groups as compared to control group. Nevertheless, in comparison to control group, NO production was profoundly increased and serum levels of MDA, CRP and ADMA were significantly decreased with atorvastatin or rosiglitazone therapy. 15-d-PGJ2 expression of myocardium was also significantly elevated with atorvastatin or rosiglitazone treatment. Notably, these effects were further enhanced with combined therapy, suggesting that atorvastatin and rosiglitazone had synergistic effects on endothelial protection, and inflammation and oxidation amelioration.
  
  
  CONCLUSIONS
  Atorvastatin and rosiglitazone therapy had synergistic effects on endothelium protection as well as amelioration of oxidative stress and inflammatory reaction in rats with dyslipidemia.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Zhang
authors.forename: Wen-Ju
authors.initials: WJ
authors.lastname: Yan
authors.forename: Bei
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Hospital of Economic and Technological Development Zone, Yantai, Shandong Province 264001, China. zouzhipeng168@yeah.net.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Zou
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050197:Atherosclerosis / Q000517:prevention & control; D000069059:Atorvastatin; D019610:Cytoprotection; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D050171:Dyslipidemias / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000069059:Atorvastatin