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Sex‐specific transcriptomic regulation in the diseased human heart
Author(s) -
Kararigas Georgios,
Summer Holger,
Baczko Istvan,
Golz Stefan,
RegitzZagrosek Vera
Publication year - 2016
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.30.1_supplement.738.9
Subject(s) - biology , wnt signaling pathway , transcriptome , dilated cardiomyopathy , gene , fibrosis , heart failure , medicine , genetics , microbiology and biotechnology , endocrinology , gene expression
Pressure overload‐induced left ventricular (LV) hypertrophy and heart failure manifest differently between men and women. Transcriptional regulation is crucial in many (patho)physiological processes. We aimed at studying the impact of sex on global gene expression in LVs of men and women with aortic stenosis (AS) and end‐stage dilated cardiomyopathy (DCM) compared with LVs of men and women with no cardiovascular disorder ( n = 5–10/group). Genome‐wide expression profiling was performed using the Affymetrix platform and the data were analyzed with R and Bioconductor considering adjusted P < 0.05 significant. In AS, fibrosis‐related genes were induced in male samples, while ribosomal and energy‐related genes were repressed. Female‐specific repressed genes in AS included extracellular matrix‐related and inflammatory genes, while members of the mitochondrial carrier protein family were induced. Similarly, pathway analysis revealed that fibrosis‐related pathways were induced in male AS samples, while inflammatory pathways were repressed in female AS samples. In DCM, male‐specific induced genes included several members of the immunoglobulin family, while a number of ribosomal and energy‐related genes were repressed. Female‐specific induced genes in DCM included those encoding several zinc finger proteins, while members of protein polyubiquitination were repressed. Pathway analysis revealed induction of ECM‐receptor interaction and inflammatory pathways in male DCM hearts, while the oxidative phosphorylation and proteasome pathways were repressed. In female DCM hearts, the Wnt and Hedgehog signaling pathways were induced, while the mTOR signaling pathway was repressed. The present findings offer an important insight into disease biology, a novel sex‐specific aspect of gene regulation in the human hypertrophied and failing heart, and may have a wide implication in the development of new and personalized therapies. Support or Funding Information DZHK (German Centre for Cardiovascular Research)