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 cardiomyocytes]. 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 cardiomyocytes]

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 the effect of local inflammatory activation on cardiomyocyte function. 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.

射血分数保留型心力衰竭（Heart failure with preserved ejection fraction, HFpEF）是一类发病率与患病率持续攀升的公共卫生问题。目前已基于相关危险因素、心脏结构改变、生物标志物及预后特征，划分出多种临床表型。其中预后最差的表型以代谢功能紊乱为核心表征。该临床表型伴随代谢失调相关生物标志物与肿瘤坏死因子-α（TNF-α）介导的炎症水平显著升高，提示其与代谢功能紊乱及炎症反应存在紧密关联。本研究旨在深入解析免疫细胞在代谢相关射血分数保留型心力衰竭发病机制中的作用，以及局部炎症激活对心肌细胞功能的影响。整体实验设计：将7~8周龄的雄性C57BL/6J（RRID:IMSR_JAX:000664）与载脂蛋白E敲除（ApoE KO, B6.129P2-Apoe tm1Unc/J）小鼠（法国查尔斯河公司）分别喂食标准饲料（CD）或高脂饲料（HFD，即高脂高胆固醇西式饮食，胆固醇含量0.21%；Sniff EF D12079），干预时长为7或。