Atorvastatin-induced endothelial nitric oxide synthase expression in endothelial cells is mediated by endoglin.

Atorvastatin-induced endothelial nitric oxide synthase expression in endothelial cells is mediated by endoglin. J Physiol Pharmacol. 2015 Jun;66(3):403-13 Authors: Zemankova L, Varejckova M, Dolezalova E, Fikrova P, Jezkova K, Rathouska J, Cerveny L, Botella LM, Bernabeu C, Nemeckova I, Nachtigal P Abstract Endoglin, a transforming growth factor β (TGF-β) receptor type III, is co-expressed with endothelial nitric oxide synthase (eNOS) in aortic endothelium in atherosclerotic plaques of mice. Interestingly, atorvastatin (ATV) is able to increase both endoglin and eNOS expression and reduce plaque size beyond its lipid lowering effects but by unknown mechanisms. We hypothesized whether inflammation modulates ATV-dependent induction of endoglin and eNOS expression in vitro in endothelial cells and whether ATV-induced eNOS expression is regulated via endoglin. After treatment of human umbilical vein endothelial cells (HUVECs) with TNF-α, endoglin and eNOS protein expression was reduced, concomitantly with increased levels of cell surface VCAM-1 and soluble endoglin, as determined by flow cytometry, Western blot and ELISA analyses. By contrast, ATV treatment increased endoglin and eNOS protein expression, while preventing TNF-α-mediated downregulation of endoglin and eNOS protein levels. Moreover, suppression of endoglin using small interfering RNA (siRNA), but not inhibition of TGF-β signaling with SB431542, abrogated ATV-induced eN...
Source: Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Tags: J Physiol Pharmacol Source Type: research