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Sex-dependent regulation of fibrosis and inflammation in human left ventricular remodelling under pressure overload

Kararigas, G. and Dworatzek, E. and Petrov, G. and Summer, H. and Schulze, T. M. and Baczkó, István (2014) Sex-dependent regulation of fibrosis and inflammation in human left ventricular remodelling under pressure overload. EUROPEAN JOURNAL OF HEART FAILURE, 16 (11). pp. 1160-1167. ISSN 1388-9842

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Abstract

AIMS: Women with aortic stenosis develop a more concentric form of LV hypertrophy than men. However, the molecular factors underlying sex differences in LV remodelling are incompletely understood. We took an unbiased approach to identify sex-specific patterns in gene expression and pathway regulation, and confirmed the most prominent findings in human hearts. METHODS AND RESULTS: Echocardiography was performed in 104 patients (53.8% women) with aortic stenosis before aortic valve replacement. LV mass, LV end-diastolic diameter, and relative wall thickness were included in a factor analysis to generate an index classifying LV remodelling as adaptive or maladaptive. Maladaptive remodelling was present in 64.6% of male and in 32.7% of female patients (P < 0.01). Genome-wide expression profiling of LV samples was performed in a representative subgroup of 19 patients (52.6% women) compared with samples from healthy controls (n = 18). Transcriptome characterization revealed that fibrosis-related genes/pathways were induced in male overloaded ventricles, while extracellular matrix-related and inflammatory genes/pathways were repressed in female overloaded ventricles (adjusted P < 0.05). We confirmed gene regulation by quantitative real-time reverse transcription-polymerase chain reaction and immunoblotting analysis, and we further demonstrate the relevance of our findings by histological documentation of higher fibrosis in men than in women. CONCLUSION: We conclude that in pressure overload distinct molecular processes are regulated between men and women. Maladaptive LV remodelling occurs more frequently in men and is associated with greater activation of profibrotic and inflammatory markers. Collectively, sex-specific regulation of these processes may contribute to sex differences in the progression to heart failure.

Item Type: Article
Additional Information: Institute of Gender in Medicine, Center for Cardiovascular Research, Charite University Hospital, Hessische Str. 34, Berlin, D-10115, Germany DZHK (German Center for Cardiovascular Research), Berlin site, Germany German Heart Institute Berlin, Germany Bayer HealthCare, Wuppertal, Germany Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Cited By :43 Export Date: 17 September 2019 CODEN: EJHFF Correspondence Address: Kararigas, G.; Institute of Gender in Medicine, Center for Cardiovascular Research, Charite University Hospital, Hessische Str. 34, Germany Chemicals/CAS: Janus kinase, 161384-16-3; myocyte enhancer factor 2, 148349-68-2; natriuretic factor, 9088-07-7; tissue inhibitor of metalloproteinase 2, 124861-55-8; RNA, 63231-63-0; RNA Institute of Gender in Medicine, Center for Cardiovascular Research, Charite University Hospital, Hessische Str. 34, Berlin, D-10115, Germany DZHK (German Center for Cardiovascular Research), Berlin site, Germany German Heart Institute Berlin, Germany Bayer HealthCare, Wuppertal, Germany Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Cited By :45 Export Date: 31 October 2019 CODEN: EJHFF Correspondence Address: Kararigas, G.; Institute of Gender in Medicine, Center for Cardiovascular Research, Charite University Hospital, Hessische Str. 34, Germany Chemicals/CAS: Janus kinase, 161384-16-3; myocyte enhancer factor 2, 148349-68-2; natriuretic factor, 9088-07-7; tissue inhibitor of metalloproteinase 2, 124861-55-8; RNA, 63231-63-0; RNA Institute of Gender in Medicine, Center for Cardiovascular Research, Charite University Hospital, Hessische Str. 34, Berlin, D-10115, Germany DZHK (German Center for Cardiovascular Research), Berlin site, Germany German Heart Institute Berlin, Germany Bayer HealthCare, Wuppertal, Germany Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Cited By :45 Export Date: 4 November 2019 CODEN: EJHFF Correspondence Address: Kararigas, G.; Institute of Gender in Medicine, Center for Cardiovascular Research, Charite University Hospital, Hessische Str. 34, Germany Chemicals/CAS: Janus kinase, 161384-16-3; myocyte enhancer factor 2, 148349-68-2; natriuretic factor, 9088-07-7; tissue inhibitor of metalloproteinase 2, 124861-55-8; RNA, 63231-63-0; RNA Institute of Gender in Medicine, Center for Cardiovascular Research, Charite University Hospital, Hessische Str. 34, Berlin, D-10115, Germany DZHK (German Center for Cardiovascular Research), Berlin site, Germany German Heart Institute Berlin, Germany Bayer HealthCare, Wuppertal, Germany Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Cited By :49 Export Date: 10 December 2019 CODEN: EJHFF Correspondence Address: Kararigas, G.; Institute of Gender in Medicine, Center for Cardiovascular Research, Charite University Hospital, Hessische Str. 34, Germany Chemicals/CAS: Janus kinase, 161384-16-3; myocyte enhancer factor 2, 148349-68-2; natriuretic factor, 9088-07-7; tissue inhibitor of metalloproteinase 2, 124861-55-8; RNA, 63231-63-0; RNA
Subjects: R Medicine / orvostudomány > RC Internal medicine / belgyógyászat
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 07 Jan 2021 16:11
Last Modified: 07 Jan 2021 16:12
URI: http://real.mtak.hu/id/eprint/119289

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