Impact of simvastatin and losartan on antiinflammatory effect: In vitro study

Antiniflammatory properties of losartan are currently unclear. This study tested the hypothesis that losartan itself has an antiinflammatory effect comparable to that of simvastatin. Human umbilical vein endothelial cells (HUVECs) were (1) incubated with culture medium alone, (2) incubated with added C-reactive protein (CRP) (25, 50, 75, and 100 mu g/mL) for stimulation, and (3) pretreated with losartan (stepwise increased dose: 100, 300, 500, and 750 mu mol/L) and simvastatin (stepwise increased dose: 25, 50, 75, and 100 mu nol/L) for 4 hours before adding CRP for stimulation. Surface expression of vascular cell adhesion molecule-1 (VCAM-1) was determined by flow cytometry. Supernatant levels of monocyte chemo-attractant protein-1 (MCP-1) and interleukin-6 (IL-6) were measured by ELISA. Experimental results showed that the effect of CRP on VCAM-l expression and supernatant levels of MCP-1 and IL-6 increases stepwise as CRP concentrations increase from 25 to 50 to 75 to 100 mu g/mL (all P < 0.001). The effect of CRP on VCAM-1 expression in HUVECs and supernatant levels of MCP-1 and IL-6 were significantly suppressed by 25 mu mol/L simvastatin with stepwise increased suppression as simvastatin dose increased to 50, 75, and 100 mu mol/L (all P < 0.0001). However, losartan did not significantly Suppress CRP's effect on VCAM-1 expression in HUVECs (P > 0.5). Moreover, losartan did not Suppress CRPs effect on MCP-1 and IL-6 secretion unless a high dose (>= 500 mu mol/L) of losartan was used. Compared with simvastatin, losartan had less effect on suppression of CRP-mediated inflammation.