Liraglutide Protects Against Diastolic Dysfunction and Improves Ventricular Protein Translation.

Area of Science:

• Cardiovascular Research
• Metabolic Disease
• Pharmacology

Background:

• Diastolic dysfunction is a growing concern, often preceding heart failure with preserved ejection fraction.
• Glucagon-like peptide 1 (GLP-1) receptor agonists show promise in treating diastolic dysfunction.

Purpose of the Study:

• To investigate the effects of liraglutide, a GLP-1 receptor agonist, on diastolic dysfunction induced by angiotensin II (AngII) in a mouse model.
• To explore the underlying physiologic and metabolic changes associated with this therapy.

Main Methods:

• Mice underwent sham, AngII, or AngII+liraglutide treatments for 4 weeks.
• Cardiac function, weight, blood pressure, histology, protein analysis, metabolomics, and protein synthesis were assessed.

Main Results:

• AngII induced diastolic dysfunction, which was partially prevented by liraglutide.
• Liraglutide treatment increased cardiac amino acid accumulation and protein turnover.
• Improved protein translation markers and synthesis were observed in liraglutide-treated mice.
• Liraglutide-treated mice experienced lean muscle mass loss.

Conclusions:

• Liraglutide protects against AngII-induced diastolic dysfunction, partly via enhanced cardiac amino acid uptake and protein turnover.
• Potential for sarcopenia and frailty necessitates long-term studies on liraglutide in diastolic disease.