INTRODUCTION
HFpEF, HF, Hashimoto, Heart failure, lower viscoelastic stiffness
HEART FAILURE, OBESE, HASHIMOTO
Heart failure (HF) is a significant public health issue, and it is the primary cause of hospitalization in Western countries (Dickstein et al., The past two decades of research have revealed several critical pathomechanisms contributing to myocardial remodeling in HFpEF, including cytoskeletal and myofilament protein‐mediated viscoelastic remodeling in response to persistent exposure to metabolic and hemodynamic stressors (Hamdani & Paulus, Geranylgeranylacetone (GGA), a related isoprenoid compound to geranylgeranylpyrophosphate (Hashimoto et al., Because small HSPs can lower viscoelastic stiffness in failing human cardiomyocytes (Franssen et al., In this study, obese 21‐week‐old ZSF1 rats were administered GGA orally for four weeks prior to sacrifice. The cardiomyocytes of treated, obese ZSF1 rats were then compared to those of 25‐week‐old untreated, obese ZSF1 rats and 25‐week‐old untreated, lean ZSF1 rats. Our data show that oral delivery of GGA significantly improves cardiomyocyte compliance in association with upregulation of myofilament‐bound HSPB1 and HSPB5. As such GGA is a promising therapeutic modality for HFpEF, adding a much‐needed treatment option to the current therapeutic approaches.