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

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 regulatio...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Kararigas Georgios
Dworatzek Elke
Petrov Gregor
Summer Holger
Schulze Tabea Marie
Baczkó István
Knosalla Christoph
Golz Sterfan
Hetzer Roland
Regitz-Zagrosek Vera
Dokumentumtípus: Cikk
Megjelent: 2014
Sorozat:EUROPEAN JOURNAL OF HEART FAILURE 16 No. 11
doi:10.1002/ejhf.171

mtmt:2763903
Online Access:http://publicatio.bibl.u-szeged.hu/16226
Leíró adatok
Tartalmi kivonat: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.
Terjedelem/Fizikai jellemzők:1160-1167
ISSN:1388-9842