کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1911988 1046854 2006 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
eNOS gene T-786C polymorphism modulates atorvastatin-induced increase in blood nitrite
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
eNOS gene T-786C polymorphism modulates atorvastatin-induced increase in blood nitrite
چکیده انگلیسی

Statins inhibit cholesterol synthesis and produce pleiotropic, cholesterol-independent effects including endothelial NO synthase (eNOS) stimulation and increased expression. However, a functional polymorphism in the promoter of the eNOS gene (T-786C) reduces its activity and could modulate the response to statins. Here, we examined whether this polymorphism modulates the effects of atorvastatin on the plasma levels of markers of NO formation and oxidative stress. We genotyped 200 healthy subjects for this polymorphism, and 15 subjects with the TT genotype and 15 with the CC genotype were selected to receive placebo or atorvastatin 10 mg/day po for 14 days. To assess NO bioavailability, the plasma concentrations of nitrate, nitrite, and cGMP and the whole blood nitrite concentrations were determined after placebo or atorvastatin using an ozone-based chemiluminescence assay and an enzyme immunoassay. Thiobarbituric acid-reactive species (TBA-RS) were measured in the plasma to assess oxidative stress. Atorvastatin decreased cholesterol concentrations independent of genotype. Whereas atorvastatin produced no significant changes in plasma nitrite, nitrate, or cGMP concentrations in both genotype groups, atorvastatin increased whole blood nitrite concentrations and decreased plasma TBA-RS concentrations in the CC (but not in the TT) genotype group. These findings suggest that the T-786C polymorphism modulates the effects of atorvastatin on NO bioavailability and oxidative stress.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 41, Issue 7, 1 October 2006, Pages 1044–1049
نویسندگان
, , , , , ,