Sex Hormones and Cardiomyopathic Phenotype Induced by Cardiac β2-Adrenergic Receptor Overexpression
| Autor: | Elodie Percy, Alex Agrotis, Garry L. Jennings, Elizabeth A. Woodcock, Xiao-Jun Du, Xiao-Ming Gao, Anthony M. Dart, Dominic J. Autelitano |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Cardiomyopathy Gene Expression Blood Pressure Mice Transgenic Biology Muscle hypertrophy Transforming Growth Factor beta1 Mice Ventricular Dysfunction Left chemistry.chemical_compound Endocrinology Heart Rate Transforming Growth Factor beta Internal medicine medicine Animals Orchiectomy Survival rate Testicular Hormones Ultrasonography Sex Characteristics Myosin Heavy Chains Ventricular Remodeling Body Weight Estrogens medicine.disease Mice Inbred C57BL Survival Rate Phenotype Castration chemistry Heart failure Androgens Female Receptors Adrenergic beta-2 Cardiomyopathies Hormone |
| Zdroj: | Endocrinology. 144:4097-4105 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2002-0214 |
| Popis: | Sex differences in cardiomyopathic phenotype and the role of gonadal status were studied in mice with cardiac overexpression of beta(2)-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 beta(2)-AR overexpression at a high level leads to cardiomyopathy and heart failure with aging. Female mice had less cardiac remodeling, dysfunction, and pathology and a marked survival advantage over male mice, and this was independent of prevailing levels of ovarian hormones. TG males showed benefit from orchiectomy, suggesting a contribution by testicular hormones to the progression of the cardiomyopathic phenotype. |
| Databáze: | OpenAIRE |
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