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

Endoglin, a transforming growth factor ß (TGF-ß) 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-ß signaling with SB431542, abrogated ATV-induced eNOS expression. These results suggest that ATV treatment prevents inflammation-reduced endoglin and eNOS expression in endothelial cells and that ATV-induced eNOS expression strongly depends on the proper expression of endoglin in HUVECs. Possible implications of these findings might be reflected in pathological conditions characterized by reduced expression of endoglin and eNOS as for example in hereditary hemorrhagic telangiectasia or in other endothelial dysfunctions.

[Visual evoked potentials in chronic alcoholics]. / Vysetrení zrakových evokovaných potenciálu u chronických alkoholiku.

In 25 chronic alcoholics (24 men, 1 women, mean age 45 years, mean period of abuse 26 years) the authors examined visual evoked potentials to stimulation by checkerboard pattern reversal. The results were compared with findings in a control group of 46 healthy subjects. An abnormal finding as regards the VEP was recorded in 28% of the alcoholics. The differences comprised a prolongation of the latency and poorer reproducibility and differentiation ability of the evoked complex which frequently had an atypical shape. On the other hand, the mean amplitude of VEP in the two groups did not differ significantly. There was no difference as regards mean age and mean period of abuse between alcoholics with a normal and abnormal VEP finding. All alcoholics who after successful treatment abstained for at least three months had a normal VEP finding. This may suggest a relative reversibility of VEP changes in chronic alcoholics, assuming treatment and abstinence. The authors did not prove any effect of Antabuse on VEP.