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Sex‐Specific Calcium Handling Underlying Sex‐Specific Cardiomyocyte Death in Heart Failure
Author(s) -
Kararigas Georgios,
Molina Cristina,
Summer Holger,
Baczko Istvan,
Golz Stefan,
RegitzZagrosek Vera
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.555.2
Subject(s) - heart failure , medicine , endocrinology , wnt signaling pathway , biology , signal transduction , microbiology and biotechnology
Heart failure manifests differently between men and women and there are major sex differences in cardiomyocyte death. We aimed at studying the impact of sex on global gene expression in left ventricles of male ( n = 5) and female ( n = 5) patients with end‐stage dilated cardiomyopathy (DCM) compared with samples of men ( n = 10) and women ( n = 8) with no cardiovascular disorder. Pathway analysis (adjusted P < 0.05) revealed induction of ECM‐receptor interaction and inflammatory pathways in male hearts, while the oxidative phosphorylation and proteasome pathways were repressed. In contrast, the Wnt and Hedgehog signaling pathways were induced in female hearts, while the mTOR signaling pathway was repressed. The Ca2+ pathway was induced in both male and female hearts, but male hearts had a significantly higher induction. In isolated human ventricular myocytes (HVMs) from DCM patients, we found by patch‐clamp a 2‐fold increase in L‐type Ca2+ current density in male vs. female HVMs ( n = 6‐8 cells/group), while there were no sex differences in sarcoplasmic reticulum Ca2+ load. Cytochrome c cytosolic release was significantly higher in male than female hearts ( P < 0.05), while female hearts had significantly higher BCL2 protein levels than male hearts ( P < 0.05). In conclusion, there are major sex differences in Ca2+ handling in the failing heart, which may be part of the molecular factors underlying sex differences in heart failure.