17β-estradiol improves survival in male mice with cardiomyopathy induced by cardiac-specific tumor necrosis factor-α overexpression

A transgenic mouse model of congestive heart failure (CHF) consequent to cardiac-specific overexpression of tumor necrosis factor-alpha (TNF-alpha) (TNF1.6) displays marked sex-related phenotypic differences. To clarify the potential contributions of estrogen to these sex-specific differences, male TNF1.6 mice were treated with 17 beta-estradiol (E-2). E-2 treatment started at 25 +/- 1 days old (group A), but not at 36 +/- 2 days old ( group B), significantly improved survival rate (p < 0.05). Furthermore, ventricular weight/body weight ratio was significantly decreased by E-2 treatment in group A (p < 0.05). Echocardiography revealed that E-2-treated hearts in group A exhibited less left ventricular dilatation (p < 0.05) relative to untreated male TNF1.6 mice ( control). Moreover, in group A, E-2 treatment partially reversed basal and isoproterenol-stimulated fractional shortening in TNF1.6 mice (p < 0.05). The cardiac content of TNF-alpha and interleukin-1 beta (IL-1 beta) was not changed by E-2 treatment regardless of the timing of treatment. Thus, E-2 exposure prior to puberty can limit the severity of cardiomyopathy in male TNF1.6 mice.