BackgroundInflammation and endothelial dysfunction is implicated in the atherosclerosis initiation and progression in the setting of hyperlipidemia. Colchicine is a potent anti-inflammatory agent and whether colchicine combined with atorvastatin has synergistic effects on inflammation amelioration and endothelial function improvement is unknown.MethodsHyperlipidemic rat model was produced by high-fat and high-cholesterol diet for 6 weeks. Rats with normal diet were served as shame group. In hyperlipidemic group, normal saline, atorvastatin (10 mg/kg body weight/day), colchicines (0.5 mg/kg body weight/day), or atorvastatin combined with colchicines (same dosages) were prescribed for 2 weeks. Serum levels of lipid profile, C-reactive protein (CRP), liver enzyme, lipoprotein associated phospholipase A2 (Lp-PLA2) and nitric oxide (NO) production were serially assessed.ResultsBefore the beginning of the study, all laboratory variables were comparable among each group. After 6 weeks of hyperlipidemic model production, serum levels of cholesterols, CRP and Lp-PLA2 were significantly increased when compared to sham group, whereas NO production was reduced. With 2 weeks of colchicine therapy, serum levels of CRP and Lp-PLA2 were decreased and NO production was enhanced in the colchicine group in a lipid-lowering independent manner. Added colchicine into atorvastatin therapy further improved NO production and decreased CRP and Lp-PLA2 levels, indicating a potential synergism of colchicine and atorvastatin.ConclusionColchicine combined with atorvastatin may have stronger protective effects on improving endothelial function and ameliorating inflammation in rats with hyperlipidemia.

BackgroundRho kinase over-activation is associated with nitric oxide (NO) reduction and atherosclerosis. Metformin is favorable for endothelial function improvement and cardiovascular outcomes. Whether cardio-protective effect of metformin is associated with Rho kinase activity is unknown.MethodsHyperlipidemia model of rats were established accordingly. Thereafter, medical interventions in terms of atorvastatin, metformin or combined therapy were administered for 4 weeks. Laboratory parameters were compared among each groups at initial, 6 weeks of high-fat and high-cholesterol diet administration, and 4 weeks of medical intervention. Lineal regression analyses were performed.ResultsNo significant difference of laboratory parameters was observed initially. Six weeks of high-fat and high-cholesterol diet administration, serum levels of cholesterol, C-reactive protein (CRP) level, and Rho kinase activity were significantly increased while NO production was concomitantly reduced in comparison to the sham group. After 4 weeks of medical intervention, CRP level and Rho kinase activity were profoundly diminished while NO production was significantly enhanced in the atorvastatin and metformin groups, and these benefits were further enhanced with combined therapy. Lineal regression analyses showed that Rho kinase activity was negatively correlated with NO production but positively correlated with CRP level.ConclusionIn rats with hyperlipidemia, metformin and atorvastatin therapy is favorable for NO production and CRP reduction, which might be associated with Rho kinase activity decrease.

Background: Atorvastatin and poly-unsaturated fatty acid (PUFA) are beneficial for lipid-modification, whether atorvastatin plus PUFA could confer better improvement on dyslipidemia and endothelium function is unknown. Methods: Dyslipidemia model of 40 rabbits were produced with atherogenic diet, and thereafter saline, atorvastatin, PUFA, or atorvastatin plus PUFA were prescribed for 1 week. Ten rabbits given normal diet served as the sham group. Parameters of interest including lipid profiles, endothelium function (nitric oxide, NO) and activation (solution vascular-cellular adhesion molecule, (sVCAM) and intracellular adhesion molecule, (sICAM)), markers of inflammation (C-reactive protein, CRP) and oxidation (malondialdehyde, MDA) were compared among groups. Results: There was no significant difference of parameters among groups at the initial. With 1 week of atherogenic diet administration, serum levels of lipid profiles, sVCAM and sICAM, CRP and MDA were significantly increased, accompanying with profound NO reduction, as compared to the sham group. After 1 week of medical intervention, as compared to the control group (saline administration), dyslipidemia and endothelium function were modestly improved with either atorvastatin or PUFA therapy. Nevertheless, these efficacies were further and significantly enhanced with combined therapy when compared to the control group (p < 0.005), suggesting that there was synergistic effects of atorvastatin and PUFA co-therapy in rabbits with dyslipidemia. Conclusion: Atorvastatin plus PUFA therapy could immediately contribute to better improvement of lipid-modification and endothelium function in rabbits with dyslipidemia.