Single-Cell Transcriptomic Profiling of Heart Reveals ANGPTL4 Linking Fibroblasts and Angiogenesis inHeart Failure with Preserved Ejection Fraction [bulk RNA-seq]

Heart failure with preserved ejection fraction (HFpEF) is a complex, heterogeneous disease involving multiple cellular lineages and mechanisms. Here, we aimed to characterize the cellular heterogeneity and potential mechanisms of HFpEF at single-cell resolution. Overall design: Eight-week-old male C57BL/6N mice were randomly divided into two groups: an HFpEF group administered with a high-fat diet and N-nitro-L-arginine methyl ester (L-NAME, 0.5 g/L in drinking water) and a control group fed on normal diet and water. Both groups were exposed to a 12-h light/dark cycle daily. After 5 weeks, cardiac ultrasound was conducted to assess the mice's ejection fraction and diastolic function. Then, mice were euthanized by excess inhalation of CO2, followed by the isolation of the hearts and the removal of atrial tissue. Three and five ventricular samples for single-cell sequencing and bulk RNA-seq. respectively, were then obtained from each group. IMPORTANT: Please note that there was an inconsistency when referring to the control group, i.e., control group vs. CON. To avoid confusion, I have used “control group” consistently throughout the manuscript.