Sex hormones and cardiomyopathic phenotype induced by cardiac β2-adrenergic receptor overexpression

Sex differences in cardiomyopathic phenotype and the role of gonadal status were studied in mice with cardiac overexpression of β2-adrenergic receptors (ARs) over 6–15 months (mo) of age. Survival to 15 mo was 96% in wild-type mice but was poorer in transgenic (TG) mice and lower for males than females (13% vs. 56%, P < 0.001). Echocardiography demonstrated progressive left ventricular (LV) dilatation and reduction in LV fractional shortening in male but much less marked changes in female TG mice. Incidences of atrial thrombosis, pleural effusion and lung congestion were higher and myocyte size and fibrosis in the LV were greater in TG males than females. Deprivation of testicular hormones by castration during 3–15 mo of age improved survival and significantly ameliorated LV dysfunction, remodeling, and hypertrophy compared with intact TG males. No significant effect, except for a trend of a better survival, was detected by ovariectomy in TG females. In conclusion, cardiac β2-AR overexpression at a high l...