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Estrogen regulation of TNF‐[alpha] in adverse myocardial remodeling is cardioprotective
Author(s) -
McLarty Jennifer L,
Gardner Jason L,
Janicki Joseph S,
Brower Gregory L
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1032.8
Subject(s) - medicine , cardioprotection , estrogen , ovariectomized rat , heart failure , endocrinology , cardiac function curve , adverse effect , ventricular remodeling , cardiology , fistula , diastole , myocardial infarction , blood pressure , surgery
Our laboratory has previously reported significant increases in TNF‐α levels are acutely induced in male hearts in the rat infrarenal aortocaval fistula model of heart failure. Elevated levels of TNF‐α in males are accompanied by left ventricular (LV) dilatation and cardiac dysfunction. In contrast, the extent of adverse LV remodeling is markedly attenuated in intact female rats post‐fistula. Therefore, we sought to determine whether estrogen modulation of TNF‐α contributes to this gender related cardioprotection. Eight week old ovariectomized female (N=10) and male (N=10) Sprague Dawley rats were treated with estrogen (0.02 mg/kg per day) beginning two‐weeks prior to fistula surgery and continued for the duration of the study. Measurements of cardiac function (diastolic and systolic) were obtained using our blood‐perfused isolated heart preparation at eight weeks post‐fistula. LV TNF‐α mRNA and protein levels determined by RT‐PCR and ELISA at three days post‐fistula were significantly lower in estrogen treated rats relative to the untreated groups. Estrogen treatment also attenuated the subsequent significant increase in LV end diastolic volume in untreated fistula groups. These data indicate that estrogen mediated attenuation of adverse myocardial remodeling can be attributed to prevention of increases in myocardial TNF‐α, thereby preventing LV dilatation and maintaining cardiac function.