Effect of an estrogen/statin combination on biochemical markers of endothelial function in human coronary artery cell cultures

Objective: The combination of an estrogen with a statin for therapy of post menopausal women is of interest because both substance classes exert benefi cial effects on the lipid profile. However, both substance classes also eli cit positive direct effects on the vasculature. Therefore in the present in vitro study an estrogen/statin combination was investigated for its effect on biochemical markers of endothelial function. Material and Methods: In endothelial cell cultures from human coronary arte ries, the effect of estradiol/fluvastatin alone and in equimolar combinatio ns, were tested at the concentrations 0.01, 0.1, and 1 muM. The vasodilator prostacyclin, the vasoconstrictor endothelin, endothelial nitric oxide syn thase (responsible for synthesis of the vasodilator nitric oxide), the proc oagulatory factor plasminogen activator inhibitor-1, and the monocyte chemo attractant protein were chosen as markers. Results: The estradiol/fluvastatin combination was able to increase prostac yclin production (25-100%) in an additive manner. The reduction of endothel in synthesis in the range of 21-46% was higher with the combination than wi th the monosubstances; the reduction, however, was not statistically signif icant. The expression of endothelial nitric oxide synthase was not signific antly increased by the combination compared with the monosubstances, howeve r, a tendency to an additive increase was observed. For the synthesis of pl asminogen activator inhibitor-1, no significant changes were seen for eithe r the monosubstances or the combination. The synthesis of monocyte chemoatt ractant protein-1 was decreased by the combination between 21% and 40%; the decrease, however, was not statistically significant compared with the eff ect of the monosubstances. The effective estradiol concentrations are highe r than can be achieved by replacement therapy; in contrast, fluvastatin was effective at concentrations that can be reached during clinical treatment. Conclusions: These results indicate that an estrogen/statin combination exe rts beneficial effects on the vasculature that seem to be superior to the e ffects of the monosubstances. The changes found for the biochemical markers can improve endothelial function. The presented results should encourage t he performance of clinical studies in cardiovascular risk patients with est rogen/statin combinations.