R. A. Farris, C. Wiley, E. T. Price; University of Arkansas for Medical Sciences, Little Rock, ARBACKGROUND:
Growing evidence suggests that intensive statin therapy is associated with paradoxical increases in cardiovascular risks. Intrigued by these findings, we examined the effects of the two most commonly used intensive statins with and without fenofibrate in a cell model of cardiovascular disease (CVD).METHODS:
Human umbilical vein endothelial cells (HUVECs) were treated with simvastatin or atorvastatin, both with and without fenofibrate (10 μM) or experimental CVD conditions (IL1β 2ng/mL). Cytokines were measured from the cell culture supernates by ELISA and gene expression analyses were conducted via RT-PCR. One-way ANOVA was conducted with correction for multiple comparisons where appropriate.RESULTS:
Cotreatment with simvastatin and fenofibrate led to a paradoxical increase in MCP-1 and ENA-78 in HUVECs whereas cotreatment with atorvastatin reduced these inflammatory markers. Gene expression analyses identified induction of RELA (p65 subunit of NFκB) as a contributor to the paradoxical pro-inflammatory response.CONCLUSION:
Simvastatin and atorvastatin displayed differential effects on inflammation and which may contribute to the adverse drug responses associated with intensive statin therapy.