Female rats with severe left ventricle volume overload exhibit more cardiac hypertrophy but fewer myocardial transcriptional changes than males

Catherine Beaumont,Marie Arsenault,Élise Roussel,Élisabeth Walsh-Wilkinson,Marie-Claude Drolet,Jacques Couet

doi:10.1038/s41598-017-00855-9

Catherine Beaumont, Marie Arsenault + Show 4 more

Open Access

https://doi.org/10.1038/s41598-017-00855-9

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Abstract

Aortic valve regurgitation (AR) imposes a volume overload (VO) to the left ventricle (LV). Male rats with a pathological heart overload usually progress more quickly towards heart failure than females. We examined whether a sexual dimorphism exists in the myocardial transcriptional adaptations to AR. Adult Wistar male and female rats either underwent a sham operation or were induced with AR and then followed for 26 weeks. Female AR rats gained relatively more LV mass than males (75 vs. 42%). They had a similar increase in LV chamber dimensions compared to males but more wall thickening. On the other hand, fatty acid oxidation (FAO)-related LV enzyme activity was only decreased in AR males. The expression of genes encoding FAO-related enzymes was only reduced in AR males and not in females. A similar situation was observed for the expression of genes involved in mitochondrial biogenesis or function as well as for genes encoding for transcription factors implicated in the control of bioenergetics and mitochondrial function (Errα, Errγ or Pgc1α). Although females develop more LV hypertrophy from severe VO, their myocardial gene expression remains closer to normal. This could provide survival benefits for females with severe VO.

Highlights

Cardiac hypertrophy (H) is used as a prognostic indicator of progression towards heart failure (HF)
ArF (n = 7/8) 353 ± 15.3b 1563 ± 101.1a, b 4.4 ± 0.12a, b 1094 ± 66.0a, b 3.1 ± 0.23a, b 320 ± 40.4a, b 0.90 ± 0.133a, b 2.3 ± 0.5b model, we observed that females developed more LVH than males and that removing oestrogens by performing an ovariectomy did not influence LVH development[14]. In both pre-clinical pressure overload (PO) and volume overload (VO) rodent models, the development of HF seems to be slower in females, but this may not be directly linked to levels of cardiac hypertrophy
The relative left and right ventricle (RV) weights indexed for body weight were increased more in female aortic valve regurgitation (AR) rats than in males (LV: 82% vs. 64% and RV: 70% vs. 38%, respectively)

Summary

Introduction

Cardiac hypertrophy (H) is used as a prognostic indicator of progression towards heart failure (HF). In pressure overload (PO) diseases such as aortic valve stenosis or arterial hypertension, female patients usually develop more LVH, they have better EF and less myocardial fibrosis than male patients[3, 4]. Male mice with transverse aortic constriction (TAC; a PO model) develop concentric LVH sooner than females[7]. In the aortic valve regurgitation (AR) rat www.nature.com/scientificreports/ In both pre-clinical PO and VO rodent models, the development of HF seems to be slower in females, but this may not be directly linked to levels of cardiac hypertrophy. We demonstrate that LV gene expression in rats with severe AR is significantly less altered in females, they developed significantly more cardiac hypertrophy than males

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