Fachbereich Veterinärmedizin



    Steroidal and Nonsteroidal Mineralocorticoid Receptor Antagonists Cause Differential Cardiac Gene Expression in Pressure Overload-Induced Cardiac Hypertrophy (2016)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Grune, Jana
    Benz, Verena
    Brix, Sarah
    Salatzki, Janek
    Blumrich, Annelie
    Höft, Beata
    Klopfleisch, Robert (WE 12)
    Foryst-Ludwig, Anna
    Kolkhof, Peter
    Kintscher, Ulrich
    Journal of cardiovascular pharmacology; 67(5) — S. 402–411
    ISSN: 0160-2446
    URL (Volltext): http://journals.lww.com/cardiovascularpharm/pages/articleviewer.aspx?year=9000&issue=00000&article=98824&type=abstract
    DOI: 10.1097/FJC.0000000000000366
    Pubmed: 26859196
    Institut für Tierpathologie

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    Abstract / Zusammenfassung

    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 due to side effects. Recently, a new highly selective and potent, non-steroidal 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 w after TAC using a pathway-focused qPCR 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 LV mass (LVM) 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 non-steroidal MR-antagonism by FIN on LVM development in pressure overload associated with a distinct cardiac gene expression profile.