title: Steroidal and Nonsteroidal Mineralocorticoid Receptor Antagonists Cause Differential Cardiac Gene Expression in Pressure Overload-induced Cardiac Hypertrophy.
abstract: Pharmacological blockade of mineralocorticoid receptors (MR) is known as an efficacious therapy in chronic heart failure. Therapy with steroidal MR antagonists such as spironolactone or eplerenone (EPL) is often limited because of side effects. Recently, a new highly selective and potent, nonsteroidal MR antagonist, finerenone (FIN), has been developed. To investigate the effects of FIN on pressure-induced cardiac hypertrophy, the transverse aortic constriction (TAC) model was used in C57BL/6 mice treated with FIN (10 mg·kg·d), EPL (200 mg·kg·d) or vehicle (VEH). First, we analyzed cardiac gene expression 4 weeks after TAC using a pathway-focused quantitative polymerase chain reaction array. FIN caused a distinct cardiac gene expression profile compared to VEH and EPL, including differential expression of BNP (brain natriuretic peptide) and Tnnt2 (troponin T type 2). FIN treatment led to a significant reduction of TAC-induced left ventricular (LV) wall thickening assessed by echocardiography. In accordance, FIN-treated mice showed a significant lower increase of calculated left ventricular mass compared with VEH- and EPL-treated mice (FIN: 28.4 ± 3.7 mg; EPL: 38.4 ± 4.3 mg; VEH: 39.3 ± 3.1 mg; P < 0.05). These data show beneficial effects of nonsteroidal MR antagonism by FIN on left ventricular mass development in pressure overload associated with a distinct cardiac gene expression profile.
authors: *Institute of Pharmacology, Center for Cardiovascular Research, Charité-Universitaetsmedizin Berlin, Berlin, Germany; †Department of Veterinary Pathology, College of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany; ‡DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany; and §Department of Cardiology Research, Bayer Health Care, Wuppertal, Germany.
authors: Jana
authors: J
authors: Grune
authors: Verena
authors: V
authors: Benz
authors: Sarah
authors: S
authors: Brix
authors: Janek
authors: J
authors: Salatzki
authors: Annelie
authors: A
authors: Blumrich
authors: Beata
authors: B
authors: Höft
authors: Robert
authors: R
authors: Klopfleisch
authors: Anna
authors: A
authors: Foryst-Ludwig
authors: Peter
authors: P
authors: Kolkhof
authors: Ulrich
authors: U
authors: Kintscher
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D000077545:Eplerenone; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009287:Naphthyridines / Q000494:pharmacology*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D020107:Troponin T / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D009287:Naphthyridines; D020107:Troponin T; C576501:finerenone; D020097:Natriuretic Peptide, Brain; D013148:Spironolactone; D000077545:Eplerenone