Aromatase Deficiency Influences the Acute Response to Myocardial Ischaemic Insult in Female Mice—A Matter of Local Sex Steroid Balance?

Abstract

Sex differences exist in ischaemic heart disease, and the conventional view is that estrogen confers cardioprotection. Oestrogen synthesis depends on androgen availability, with aromatase regulating conversion of testosterone toestradiol. Extra-gonadal aromataseexpression has been shown to mediate estrogen production in some tissues, but a role for local steroid conversion has not yet been demonstrated in the heart. The aim of this study was to determine whether aromatase deficiency influences myocardial function and ischaemic resilience. RT-PCR analysis of C57Bl/6 mouse hearts confirmed cardiac-specific aromatase expression in adult females. Functional performance of isolated hearts from female aromatase knockout (ArKO) and wild-type (ArWT) mice were compared. In aerobic perfusion, left ventricular developed pressures (LVDP) were similar, but dP/dt max was modestly reduced in ArKO hearts (4272± 154mmHg/s vs 3725± 144mmHg/s, of cardiac ischaemia. In this study, we documented the release of BNP-SP and high sensitivity troponin T (Trop T hs) during dobutamine stress echocardiography (DSE) in those with coronary artery disease (CAD) and healthy volunteers. Methods: Sixteen patients withCADand 10 healthy volunteers were recruited. Plasma samples were collected just prior to the DSE and then half hourly for a total of four hours after DSE. At each time point, BNP-SP levelswere determinedby our published radioimmunoassay, whereas Trop T hs levels were determined on a Roche Elecsys analyser. Results:Themajority of patientswithCAD remained on anti-anginals including B blockers at the time of the DSE (11/16). A clear significant rise was seen in both groups in both markers above the 99th percentile upper normal range (25 pmol/l for BNP-SP and 14pg/ml for Trop T hs). The two markers had very different temporal profiles of release with BNPSP peaking at 0.5 h, whereas Trop T hs peaked at 3.5–4.0 hours. There was no significant difference in the pattern of release between groups for either marker as determined by two way repeat ANOVA analysis (BNP-SP, P= 0.34; Trop T hs, P= 0.34).