Journal article
Myocardial and cardiomyocyte stress resilience is enhanced in aromatase-deficient female mouse hearts through CaMKIIδ activation
JR Bell, GB Bernasochi, AC Wollermann, AJA Raaijmakers, WC Boon, ER Simpson, CL Curl, KM Mellor, LMD Delbridge
Endocrinology United States | ENDOCRINE SOC | Published : 2015
DOI: 10.1210/en.2014-1700
Abstract
The role of sex steroids in cardioprotection is contentious, with large clinical trials investigating hormone supplementation failing to deliver outcomes expected from observational studies. Mechanistic understanding of androgen/estrogen myocardial actions is lacking. Using a genetic model of aromatase tissue deficiency (ArKO) in female mice, the goal of this investigation was to evaluate the capacity of a shift in cardiac endogenous steroid conversion to influence ischemia-reperfusion resilience by optimizing cardiomyocyte Ca2+ handling responses. In isolated normoxic cardiomyocytes, basal Ca2+ transient amplitude and extent of shortening were greater in ArKO myocytes, with preservation of ..
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Funding Acknowledgements
Career support provided through the National Heart Foundation of Australia and University of Melbourne R. Douglas Wright Faculty Trust (to J.R.B.). Research support was provided through a Grant-in-Aid from the National Heart Foundation of Australia (to L.M.D.D., J.R.B., and C.L.C.).