Heart failure with preserved ejection fraction (HFpEF) is a public health burden associated to diastolic dysfunction with no effective treatment mostly affecting elderly women. We use the Tgβ3 rats to explore the potential impact of phytoestrogen in the development of this pathology as Tgβ3 females does not develop HFpEF with ageing while Tgβ3 male with a phytoestrogen-free diet does.

The aim of our study was to evaluate phytoestrogen impact on HFpEF development.

HFpEF development has been evaluated in males and females, ovariectomized or not, with or without a phytoestrogen-free diet. HFpEF was validated by echography study (E/A ratio), invasive hemodynamic study (LVEDP) and fibrosis. Then the heart was harvested to evaluated HFpEF impact on protein expression involved on cardiac metabolism and endothelial function.

HFpEF was not established in rats with phytoestrogen diet (males and females, ovariectomized or not) and also in female's groups feed with phytoestrogen-free diet. In males with phytoestrogen-free diet, phenotype evaluation revealed diastolic dysfunction with significant modification of E/A ratio and LVEDP in Tgβ3 rats with ageing (E/A: +15% vs WT and LVEDP: +109% vs WT; P<0.05), a myocardial fibrosis with an increase of collagen I and III deposits, an endothelial dysfunction and impaired exercice tolerance at 45 weeks of age, characteristics of HFpEF. In rats developing HFpEF, a significant decrease in eNOS expression (-30% vs WT; P<0.05) was reported while rat fed with phytoestrogen diet, eNOS expression was significantly increased (+62% vs WT; P<0.05).

We demonstrated that long term exposure to oestrogen or phytoestrogen in our model is protective against the development of HFpEF but the mechanism remains unclear. Our results highlight the potential role of eNOS in HFpEF development.