Of Mice and (Hopefully) Men (and Women): Finasteride Improves Pathologic Ventricular Remodeling and Heart Failure | Journal Scan
Does anti-androgenic therapy with finasteride (which inhibits the generation of dihydroxytesterone [DHT] by the enzyme 5-α reductase) improve pathologic ventricular remodeling and heart failure in mice?
Pressure overload was induced in mice with transverse aortic constriction (TAC). After 1 week of pressure induction, mice were treated with finasteride for 2 weeks. Cardiac function, hypertrophy, dilation, and fibrosis were assessed in treated and untreated mice. The authors also assessed the expression of all three isoforms of the 5-α reductase enzyme in different pathological conditions associated with cardiomyocyte hypertrophy. In mice treated with TAC or sham surgery, expression of DHT responsive genes (Mt1, Odc1, and Axin1 mRNA) was assessed. The impact of finasteride was also assessed in advanced myocardial disease by starting therapy 21 days after TAC or sham surgery and continuing for 32 days. And, the impact of finasteride on Gαq transgenic mice (a model of cardiac failure with pronounced ventricular dilatation) was determined.
The authors made the following key observations: 1) All three isoforms of the 5-α-reductase enzyme were induced in cardiac hypertrophy (finasteride sensitive Srd5a3 was predominant in the heart); 2) Finasteride attenuated the myocardial induction of Mt1, Odc1, and Axin1 after TAC in female mice; 3) Finasteride inhibited cardiomyocyte hypertrophy; 4) Finasteride inhibited cardiac hypertrophy in mice treated with TAC, compared to those who were not treated, by reducing heart weight/body ratio, cardiomyocyte cross-sectional area, and blunted regulation of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) mRNA expression; 5) Finasteride treatment improved left ventricular systolic function and reduced cardiac dilatation; and 6) Cardiac remodeling was positively affected in both male and female mice.
The authors concluded that in mice, finasteride (which inhibits the production of DHT by the enzyme 5-α reductase) reversed pathological cardiac hypertrophy and dysfunction.
This is an interesting study that draws attention to the potential value of finasteride in relieving pathological cardiac hypertrophy associated with increased DHT levels in the myocardium. The authors demonstrate that the mechanism through which finasteride decreases DHT may be inhibition of Akt-dependent pro-hypertrophic signaling, although they caution that finasteride may exert its impact independent of its influence on 5-α-reductase. Future studies should evaluate the utility of finasteride in the treatment of heart failure in humans.
Keywords: Cardiomyopathies, Heart Failure, Atrial Natriuretic Factor, Cardiomegaly, Finasteride, Mice, Transgenic, Myocytes, Cardiac, Natriuretic Peptide, Brain, Protein Isoforms, RNA, Messenger, Ventricular Remodeling
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