Abstract 15850: Sex-specific Transcriptional and Protein Regulation of Calcium Handling Leading to Sex Differences in Cardiomyocyte Death in Heart Failure

Mechanisms underlying sex differences in heart failure (HF) are poorly understood. Women appear to have better prognosis underlain by lower rates of apoptosis and necrosis than men. We hypothesized significant sex differences in left ventricular (LV) transcriptional and protein regulation of end-stage non-ischemic dilated cardiomyopathy (DCM) patients. We compared LV samples of age- and medication-matched male (n = 5) and female (n = 5) DCM patients with male (n = 10) and female (n = 8) controls. Pathway analysis of genome-wide expression profiling (adjusted P < 0.05) revealed induction of ECM-receptor interaction and several inflammatory pathways in male LVs, while oxidative phosphorylation and proteasome pathways were repressed. In female LVs, the Wnt and Hedgehog signaling pathways were induced, while the mTOR signaling pathway was repressed. Ca2+ signaling pathway was induced in both sexes. However, male LVs had a significantly higher induction of ca. 30% of genes encoding ion channels, accessory beta...