Androgens contribute to sex differences in myocardial remodeling under pressure overload by a mechanism involving TGF-β
EstadísticasView Usage Statistics
Full recordShow full item record
AuthorMontalvo Silva, Cecilia de; Villar Ramos, Ana Victoria; Merino Fernández, David; García López, Raquel; Ares Ares, Miguel; Llano Cardenal, Miguel; Cobo Belaustegui, Manuel; Hurlé González, María Amor; Nistal Herrera, Juan Francisco
Background: In clinical studies, myocardial remodeling in aortic valve stenosis appears to be more favorable in women than
in men, even after menopause. In the present study, we assessed whether circulating androgens contribute to a less
favorable myocardial remodeling under pressure overload in males. We examined sex-related differences in one-year-old
male and female mice. Whereas male mice at this age exhibited circulating androgen levels within the normal range for
young adults, the circulating estrogens in females were reduced. The contribution of gonadal androgens to cardiac
remodeling was analyzed in a group of same-age castrated mice.
Methodology/Principal Findings: Animals were subjected to transverse aortic constriction (TAC). Echocardiography was
performed 2 weeks after TAC and myocardial mRNA levels of TGF-bs, Smads 2 and 3, collagens, fibronectin, b-myosin heavy
chain and a-myosin heavy chain were determined by q-PCR. Protein detection of p-SMAD2/3 was performed by Western
Blot. Histological staining of fibrosis was performed with picrosirius red and Masson’s trichrome. Compared with females,
males developed more severe tissue fibrosis, LV dilation and hemodynamic dysfunction. TAC-males showed higher
myocardial expression levels of TGF-bs and the treatment with a neutralizing antibody to TGF-b prevented myocardial
fibrosis development. Orchiectomy diminished TAC-induced up-regulation of TGF-bs and TGF-b target genes, and it also
reduced fibrosis and hemodynamic dysfunction. The capability of androgens to induce TGF-b expression was confirmed in
NIH-3T3 fibroblasts and H9C2 cardiomyocytes exposed to dihydrotestosterone.
Conclusions/Significance: Our results indicate that circulating androgens are responsible for the detrimental effects in the
myocardium of older male mice subjected to pressure overload through a mechanism involving TGF-bs.
Collections to which it belong
- D16 Artículos