17 Beta-estradiol improves survival in male mice with cardiomyopathy induced by cardiac-specific tumor necrosis factor-alpha 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 17beta- 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-alpha and interleukin-1beta (IL-1beta) 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.
Kadokami
Toshiaki
T
Department of Medicine, Jefferson Medical College, Philadelphia, PA 19107, USA.
McTiernan
Charles F
CF
Higuichi
Yoshihiro
Y
Frye
Carole S
CS
Kubota
Toru
T
Feldman
Arthur M
AM
D000818:Animals; D009202:Cardiomyopathies / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D002316:Cardiotonic Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000097:blood; D006352:Heart Ventricles / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D016277:Ventricular Function, Left
D002316:Cardiotonic Agents; D012739:Gonadal Steroid Hormones; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol