Excitation-contraction coupling, cardiomyocyte electrophysiology, and transcriptome profiles in two HFpEF murine models: etiology and sex-dependent differences

signaling-contraction coupling (ECC) mechanisms are fundamental to heart function. ECC mechanisms are differentially altered in murine models of heart failure with preserved ejection fraction (HFpEF) by dominant disease pathology and sex. Diastolic dysfunction is more pronounced in diabetic-obese HFpEF mice (worse in females) than in hypertensive-obese HFpEF mice (female sex is protective). Diabetic-obese mice and primarily hypertensive-obese HFpEF mice exhibit differential ECC alterations and largely distinctive transcription changes, providing mechanistic insights into HFpEF sub-phenogroups.