Molecular and Cellular Mechanisms of Heart Failure With Preserved Ejection Fraction

To understand the cellular mechanisms of heart failure with preserved ejection fraction (HFpEF), We investigated the functional outcome and the underlying mechanisms from concurrent mechanic and metabolic stresses in the heart by applying transverse aortic constriction (TAC) in lean C57Bl/6J (HFrEF phenotype) or obese/diabetic B6.Cg-Lepob/J (ob/ob) mice (HFpEF phenotype) followed by single-nuclei RNA-seq (snRNA-seq) and targeted manipulation of a top ranked signaling pathway (glucagon receptor signaling) differentially affected in the two experimental cohorts. For snRNA-seq, We collected hearts from adult male C57BL/6J or B6.Cg-Lepob/J mouse at 10 weeks post TAC injury or sham with two mice of each group. Following isolation of single nuclei from the fresh whole heart tissue, we conducted library preparation with 10x genomics 3' GEM library kit v3.1. The libraries were then sequenced on one lane of NovaSeq6000 S4 at UCLA TCGB Core. Sequencing data were then processed by Cell Ranger software and R package Seurat for dimension reduction UMAP plots, cell type annotation and differential gene expression analysis.