کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8474194 | 1550420 | 2015 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of aldosterone synthase (CYP11B2) by torasemide prevents atrial fibrosis and atrial fibrillation in mice
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کلمات کلیدی
CTGFANGIIMicrorna-21aldosterone synthase - آلدوسترون سنتازAngiotensin II - آنژیوتانسین دوLOX - اکسیژن مایعmiR-21 - به miR-21torasemide - توراسمیدLeft atrium - دهان چپLoop diuretics - دیورتیک های حلقهSinus rhythm - ریتم سینوسیConnective tissue growth factor - فاکتور رشد بافت همبندFibrosis - فیبروز یا فساد الیافAtrial fibrillation - فیبریلاسیون دهلیزیwild-type mice - موش های وحشیMineralocorticoid receptors - گیرنده های Mineralocorticoid
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Loop diuretics are used for fluid control in patients with heart failure. Furosemide and torasemide may exert differential effects on myocardial fibrosis. Here, we studied the effects of torasemide and furosemide on atrial fibrosis and remodeling during atrial fibrillation. In primary neonatal cardiac fibroblasts, torasemide (50 μM, 24 h) but not furosemide (50 μM, 24 h) reduced the expression of connective tissue growth factor (CTGF; 65 ± 6%) and the pro-fibrotic miR-21 (44 ± 23%), as well as the expression of lysyl oxidase (LOX; 57 ± 8%), a regulator of collagen crosslinking. Mineralocorticoid receptor (MR) expression and activity were not altered. Torasemide but not furosemide inhibited human aldosterone synthase (CYP11B2) activity in transfected lung fibroblasts (V79MZ cells) by 75 ± 1.8%. The selective CYP11B2 inhibitor SL242 mimicked the torasemide effects. Mice with cardiac overexpression of Rac1 GTPase (RacET), which develop atrial fibrosis and spontaneous AF with aging, were treated long-term (8 months) with torasemide (10 mg/kg/day), furosemide (40 mg/kg/day) or vehicle. Treatment with torasemide but not furosemide prevented atrial fibrosis in RacET as well as the up-regulation of CTGF, LOX, and miR-2, whereas MR expression and activity remained unaffected. These effects correlated with a reduced prevalence of atrial fibrillation (33% RacET + Tora vs. 80% RacET). Torasemide but not furosemide inhibits CYP11B2 activity and reduces the expression of CTGF, LOX, and miR-21. These effects are associated with prevention of atrial fibrosis and a reduced prevalence of atrial fibrillation in mice.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 85, August 2015, Pages 140-150
Journal: Journal of Molecular and Cellular Cardiology - Volume 85, August 2015, Pages 140-150
نویسندگان
Oliver Adam, Christina Zimmer, Nina Hanke, Rolf W. Hartmann, Birgit Klemmer, Michael Böhm, Ulrich Laufs,