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Liraglutide Attenuates Aortic Valve Calcification in a High-Cholesterol-Diet-Induced Experimental Calcific Aortic

Yangzhao Zhou1, Zhaoshun Yuan1, Min Wang1

  • 1Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China.

Journal of Cardiovascular Development and Disease
|September 27, 2023
PubMed

Insights

Liraglutide treatment improved aortic valve calcification and function in a mouse model of calcific aortic valve disease (CAVD). This suggests liraglutide may be a potential therapy for CAVD.

Area of Science:

  • Cardiovascular Research
  • Pharmacology
  • Translational Medicine

Background:

  • Calcific aortic valve disease (CAVD) is a prevalent condition in the elderly, leading to significant morbidity and mortality.
  • Current therapeutic options for CAVD are limited, with no approved medications to halt its progression.
  • This study investigates the potential of liraglutide, a glucagon-like peptide-1 (GLP-1) analog, in treating experimental CAVD.

Purpose of the Study:

  • To evaluate the efficacy of liraglutide in ameliorating the pathological features of CAVD.
  • To explore the molecular mechanisms underlying liraglutide's effects on aortic valve calcification and inflammation.
  • To assess the impact of liraglutide on aortic valve function and morphology in a preclinical model.

Main Methods:

  • A high-cholesterol diet-induced mouse model of CAVD was established.
  • Mice were randomized to receive liraglutide treatment or a control.
  • Aortic valve function, morphology, calcification, fibrosis, and inflammation were assessed using echocardiography and immunohistology.
  • Plasma GLP-1 levels and inflammatory markers were quantified.
  • RNA sequencing was employed to identify liraglutide-modulated pathways.

Main Results:

  • Liraglutide treatment significantly reduced aortic valve calcification and improved valve function in CAVD mice.
  • Inflammation and fibrosis in the aortic valve were attenuated by liraglutide.
  • RNA-seq analysis revealed that liraglutide impacts myofibroblastic and osteogenic differentiation pathways.
  • Beneficial effects correlated with increased GLP-1 receptor (GLP-1R) expression.

Conclusions:

  • Liraglutide demonstrates a therapeutic effect by inhibiting aortic valve calcification in a preclinical CAVD model.
  • Liraglutide holds promise as a potential pharmacological agent for the treatment of calcific aortic valve disease.
  • Further research is warranted to explore liraglutide's clinical utility in managing CAVD.
Abstract

Keywords:
calcific aortic valve diseaseglucagon-like peptide-1glucagon-like peptide-1 receptorliraglutide

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