Liraglutide protects against diastolic dysfunction and improves ventricular protein translation

Abstract

AbstractDiastolic dysfunction is an increasingly common cardiac issue contributing to heart failure with preserved ejection fraction (HFpEF). Previous works have implicated glucagon-like peptide 1 (GLP-1) receptor agonists as potential therapies for improving diastolic dysfunction and HFpEF outcomes, though the mechanism of these benefits remains unclear. In this study, we investigated cardiac physiologic and metabolic changes in a mouse model of angiotensin II (AngII)-mediated diastolic dysfunction with or without treatment with the GLP-1 analogue liraglutide. We found that AngII-mediated diastolic dysfunction was abrogated by liraglutide therapy based on echocardiographic changes. The improvements to diastolic dysfunction were associated with broad amino acid accumulation in the heart of the AngII+Liraglutide mice that may support protein synthesis to prevent deleterious remodeling. AngII+Liraglutide mice were also found to have peripheral muscle mass loss and increased circulating amino acids, which may suggest peripheral muscle scavenging of amino acids. Therefore, while liraglutide protects against diastolic dysfunction in the short term, long-term studies are needed to evaluate safety profiles of GLP-1 analogues in diastolic disease.