Steroid hormones and heart failure – sex perspectives
Important differences exist between women and men with regard to cardiovascular disease. Sex differences have been reported in left ventricular hypertrophy, cardiac remodeling with aging, arrhythmogenic activity, and post-infarct myocardial salvage. In recent years there has been controversy about the use of steroid therapies in men and women – and the cardiovascular problems of anabolic steroid abuse have become apparent. Therapies involving mineralocorticoid block have differential cardiac effectiveness in men and women. The molecular bases for sex-related differences in myocardial disease and response to steroids are poorly understood. The goal of this research is to determine how sex steroids ( testosterone & estrogen) and mineral/glucocorticoid steroids (aldosterone, cortisol & corticosterone) regulate heart growth and function under normal and metabolic stress conditions. We investigate the early developmental origins of progression to failure in males and females– and have demonstrated that cell loss in the neonatal transition period is linked with life-long cardiac muscle cell deficit and susceptibility to autophagy. We have discovered that the enzyme responsible for converting testosterone to estrogen (aromatase) is expressed in the heart – and that regulating the expression of aromatase has acute effects on function and arrhythmogenicity. Our work investigates how the key Ca2+ signaling molecule CaMKII works differently in female and male hearts – and how this might be very important in determining post-infarct vulnerability. A number of continuing projects are built around these investigations in the Lab.
- Bell JR, Vila-Petroff M, Delbridge LM. CaMKII-dependent responses to ischemia and reperfusion challenges in the heart. Front Pharmacol 2014; 5: 96. doi: 10.3389/fphar.2014.00096. Pubmed Link
- Bell JR, Bernasochi GB, Varma U, Boon WC, Ellem SJ, Risbridger GP, Delbridge LM. Aromatase transgenic upregulation modulates basal cardiac performance and the response to ischemic stress in male mice. Am J Physiol Heart Circ Physiol 2014; 306: H1265-74. Pubmed Link
- Bell JR, Bernasochi GB, Varma U, Raaijmakers AJ, Delbridge LM. Sex and sex hormones in cardiac stress--mechanistic insights. J Steroid Biochem Mol Biol 2013; 137: 124-35. Pubmed Link
- Rickard AJ, Morgan J, Bienvenu LA, Fletcher EK, Cranston GA, Shen JZ, Reichelt ME, Delbridge LM, Young MJ. Cardiomyocyte mineralocorticoid receptors are essential for deoxycorticosterone/salt-mediated inflammation and cardiac fibrosis. Hypertension 2012; 60: 1443-50. Pubmed Link
- Bell JR, Mellor KM, Wollermann AC, Ip WT, Reichelt ME, Meachem SJ, Simpson ER, Delbridge LM. Aromatase deficiency confers paradoxical postischemic cardioprotection. Endocrinology 2011; 152: 4937-47. Pubmed Link
- Bell JR, Curl CL, Ip WT, Delbridge LM. Ca2+/calmodulin-dependent protein kinase inhibition suppresses post-ischemic arrhythmogenesis and mediates sinus bradycardic recovery in reperfusion. Int J Cardiol 2012; 159: 112-8. Pubmed Link