This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gao, X.-M. Articles by Du, X.-J. Search for Related Content PubMed PubMed Citation Articles by Gao, X.-M. Articles by Du, X.-J.

Sex Hormones and Cardiomyopathic Phenotype Induced by Cardiac ß₂-Adrenergic Receptor Overexpression

Baker Heart Research Institute and Alfred Heart Centre, Alfred Hospital, Melbourne, Victoria 8008, Australia

Address all correspondence and requests for reprints to: Xiao-Jun Du, Baker Medical Research Institute, PO Box 6492, St Kilda Road Central, Melbourne, Victoria 8008, Australia. E-mail: xiaojun.du{at}baker.edu.au.

Sex differences in cardiomyopathic phenotype and the role of gonadal status were studied in mice with cardiac overexpression of ß₂-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 ß₂-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.

This article has been cited by other articles:

				Y. Yang, Y. Ma, W. Han, J. Li, Y. Xiang, F. Liu, X. Ma, J. Zhang, Z. Fu, Y.-D. Su, et al. Age-related differences in postinfarct left ventricular rupture and remodeling Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1815 - H1822. [Abstract] [Full Text] [PDF]

				G. E. Haddad, L. J. Saunders, S. D. Crosby, M. Carles, F. del Monte, K. King, M. R. Bristow, F. G. Spinale, T. E. Macgillivray, M. J. Semigran, et al. Human cardiac-specific cDNA array for idiopathic dilated cardiomyopathy: sex-related differences Physiol Genomics, April 1, 2008; 33(2): 267 - 277. [Abstract] [Full Text] [PDF]

				C.-W. Siu, C.-Y. Yeung, C.-P. Lau, A. W C Kung, and H.-F. Tse Incidence, clinical characteristics and outcome of congestive heart failure as the initial presentation in patients with primary hyperthyroidism Heart, April 1, 2007; 93(4): 483 - 487. [Abstract] [Full Text] [PDF]

				E. D. Lekgabe, S. G. Royce, T. D. Hewitson, M. L. K. Tang, C. Zhao, X. L. Moore, G. W. Tregear, R. A. D. Bathgate, X.-J. Du, and C. S. Samuel The Effects of Relaxin and Estrogen Deficiency on Collagen Deposition and Hypertrophy of Nonreproductive Organs Endocrinology, December 1, 2006; 147(12): 5575 - 5583. [Abstract] [Full Text] [PDF]

				C. S. Samuel Relaxin: Antifibrotic Properties and Effects in Models of Disease Clin. Med. Res., November 1, 2005; 3(4): 241 - 249. [Abstract] [Full Text] [PDF]

				P. Bridgman, M. A. Aronovitz, R. Kakkar, M. I. Oliverio, T. M. Coffman, W. M. Rand, M. A. Konstam, M. E. Mendelsohn, and R. D. Patten Gender-specific patterns of left ventricular and myocyte remodeling following myocardial infarction in mice deficient in the angiotensin II type 1a receptor Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H586 - H592. [Abstract] [Full Text] [PDF]

				X.-M. Gao, H. Kiriazis, X.-L. Moore, X.-H. Feng, K. Sheppard, A. Dart, and X.-J. Du Regression of pressure overload-induced left ventricular hypertrophy in mice Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2702 - H2707. [Abstract] [Full Text] [PDF]

				C. S. Samuel, E. N. Unemori, I. Mookerjee, R. A. D. Bathgate, S. L. Layfield, J. Mak, G. W. Tregear, and X.-J. Du Relaxin Modulates Cardiac Fibroblast Proliferation, Differentiation, and Collagen Production and Reverses Cardiac Fibrosis in Vivo Endocrinology, September 1, 2004; 145(9): 4125 - 4133. [Abstract] [Full Text] [PDF]

				X.-J. Du Gender modulates cardiac phenotype development in genetically modified mice Cardiovasc Res, August 15, 2004; 63(3): 510 - 519. [Abstract] [Full Text] [PDF]

				M. C. Rhodes, F. J. Seidler, A. Abdel-Rahman, C. A. Tate, A. Nyska, H. L. Rincavage, and T. A. Slotkin Terbutaline Is a Developmental Neurotoxicant: Effects on Neuroproteins and Morphology in Cerebellum, Hippocampus, and Somatosensory Cortex J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 529 - 537. [Abstract] [Full Text] [PDF]