An inflammatory single-cell RNA sequencing signature driven by metabolic stress in a new mouse model of heart failure with preserved ejection fraction and its reversion by the SGLT2 inhibitor dapagliflozin [RNA-Seq macrophages]

Heart failure with preserved ejection fraction (HFpEF) is a public health problem with increasing incidence and prevalence. Different phenotypes have been identified based on related risk factors, cardiac structural alterations, biomarkers and prognosis. Among these, the one with the worst prognosis is characterized by metabolic dysfunction . This clinical phenotype exhibits high levels of biomarkers related to dysregulated metabolism and TNF-a–mediated inflammation, thus underlying its close association with metabolic dysfunction and inflammation. The aim of our work is to better comprehend the involvement of the immune cells in the pathogenesis of metabolic HFpEF and to determine whether treating metabolic dysfunction with SGLT2i could ameliorate HFpEF by decreasing myocardial inflammation. Overall design: 7–8-week-old male C57BL/6J (RRID:IMSR_JAX:000664) and ApoE KO (B6.129P2-Apoe tm1Unc/J) mice (Charles River, France) were fed with standard chow (CD) or a high fat (HFD) (Western diet, high fat/high cholesterol 0.21%; Sniff EF D12079) diet for 7 or. After 8 weeks, mice were randomly assigned to either treatment or control group. The treatment group received intragastric dapagliflozin (AstraZeneca) through gavage, 1.0 mg/kg/d for 12-weeks, while mice in the control group and in another group of wild-type (WT) C57BL/6J mice were given vehicle.