Differential expression of GLP1R, PCSK9, and SGLT2 in human aortic versus mitral valve tissues: exploratory findings

Shou-Quan Cheng1,2, Shuo Fu1, Nai-Feng Liu2

  • 1Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

Insights

Glucagon-like peptide-1 receptor (GLP1R), PCSK9, and SGLT2 are more expressed in aortic valves than mitral valves. While expression trends higher in calcific aortic valve disease (CAVD) tissues, this study did not confirm CAVD-specific upregulation.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Valvular Heart Disease Research

Background:

  • Calcific aortic valve disease (CAVD) is a prevalent condition lacking effective pharmacological treatments.
  • Understanding the molecular underpinnings of CAVD is crucial for developing new therapeutic strategies.
  • This study investigates the expression of key receptors and proteins in human heart valve tissues.

Purpose of the Study:

  • To compare the expression of glucagon-like peptide-1 receptor (GLP1R), PCSK9, and SGLT2 in human aortic valve (AV) and mitral valve (MV) tissues.
  • To explore the potential pathophysiological relevance of these targets in the context of valvular heart disease.
  • To analyze expression differences in calcified versus non-calcified AV tissues and in bicuspid aortic valve (BAV) subsets.

Main Methods:

  • Human AV (n=10) and MV (n=13) tissue specimens were collected from patients undergoing valve replacement surgery.
  • Immunohistochemistry (IHC) was used to assess target protein expression.
  • Von Kossa staining confirmed valvular calcification, with subgroup analyses performed on calcified/non-calcified AV tissues and BAV subsets.

Main Results:

  • Expression of GLP1R, PCSK9, and SGLT2 was significantly higher in AV tissues compared to MV tissues (P < 0.001).
  • Expression trends for these targets were higher in calcified AV specimens than non-calcified ones, but without statistical significance (P > 0.05).
  • In the BAV subgroup, calcified tissues showed significantly higher expression of all three targets compared to non-calcified tissues (P < 0.05).

Conclusions:

  • The study demonstrates differential expression of GLP1R, PCSK9, and SGLT2 between human aortic and mitral valves.
  • While expression trends suggest a link with calcification, particularly in BAV, these findings do not establish CAVD-specific upregulation.
  • Further research is needed to elucidate the precise role of these targets in the pathogenesis of calcific aortic valve disease.
Abstract

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