17β-Estradiol Improves Survival in Male Mice with Cardiomyopathy Induced by Cardiac-Specific Tumor Necrosis Factor-α Overexpression

Abstract

A transgenic mouse model of congestive heart failure (CHF) consequent to cardiac-specific overexpression of tumor necrosis factor-α (TNF-α) (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 17β- estradiol (E₂). E₂ 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 E₂ treatment in group A (p < 0.05). Echocardiography revealed that E₂-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, E₂ treatment partially reversed basal and isoproterenol-stimulated fractional shortening in TNF1.6 mice (p < 0.05). The cardiac content of TNF-α and interleukin-1β (IL-1β) was not changed by E₂ treatment regardless of the timing of treatment. Thus, E₂ exposure prior to puberty can limit the severity of cardiomyopathy in male TNF1.6 mice.