Inhibition of aldosterone synthase (CYP11B2) by torasemide prevents atrial fibrosis and atrial fibrillation in mice.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Hartmann, Rolf W
MetadataShow full item record
AbstractLoop 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 (50μM, 24h) but not furosemide (50μM, 24h) 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 (8months) with torasemide (10mg/kg/day), furosemide (40mg/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.
CitationInhibition of aldosterone synthase (CYP11B2) by torasemide prevents atrial fibrosis and atrial fibrillation in mice. 2015, 85:140-50 J. Mol. Cell. Cardiol.
AffiliationHelmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
The following license files are associated with this item:
- Increased lysyl oxidase expression and collagen cross-linking during atrial fibrillation.
- Authors: Adam O, Theobald K, Lavall D, Grube M, Kroemer HK, Ameling S, Schäfers HJ, Böhm M, Laufs U
- Issue date: 2011 Apr
- The mineralocorticoid receptor promotes fibrotic remodeling in atrial fibrillation.
- Authors: Lavall D, Selzer C, Schuster P, Lenski M, Adam O, Schäfers HJ, Böhm M, Laufs U
- Issue date: 2014 Mar 7
- Rac1-induced connective tissue growth factor regulates connexin 43 and N-cadherin expression in atrial fibrillation.
- Authors: Adam O, Lavall D, Theobald K, Hohl M, Grube M, Ameling S, Sussman MA, Rosenkranz S, Kroemer HK, Schäfers HJ, Böhm M, Laufs U
- Issue date: 2010 Feb 2
- Rac1 GTPase regulates 11β hydroxysteroid dehydrogenase type 2 and fibrotic remodeling.
- Authors: Lavall D, Schuster P, Jacobs N, Kazakov A, Böhm M, Laufs U
- Issue date: 2017 May 5
- [Effects of various diuretics on cardiac function in rats with heart failure].
- Authors: Tanaka H, Watanabe K, Harima M, Thanikachalam PV, Yamaguchi K, Tachikawa H, Kodama M, Aizawa Y
- Issue date: 2009 Jul