CTRP3 is a coronary artery calcification biomarker and protects against vascular calcification by inhibiting β-catenin nuclear translocation to prevent vascular smooth muscle cell osteogenic differentiation

J Cardiol. 2022 Apr;79(4):551-558. doi: 10.1016/j.jjcc.2021.10.018. Epub 2021 Nov 10.

Abstract

Background: Coronary artery calcification (CAC) is an important risk factor for cardiovascular events and has been shown to be correlated with serum adiponectin levels. However, it remains unknown whether C1 tumor necrosis factor-related protein 3 (CTRP3) (homologous to adiponectin) is associated with CAC, and whether CTRP3 affects the osteoblastic differentiation of vascular smooth muscle cells. Here, we analyzed the association between CTRP3 expression and CAC.

Methods: A case-control study was conducted involving 119 patients with coronary heart disease to identify the predictive value of CTRP3 for CAC. Additionally, mouse aortic smooth muscle cells transfected for β-catenin overexpression were subjected to treatment with CTRP3 and the β-catenin inhibitor JW74. The calcium content in smooth muscle cells was determined. Western blotting was performed to measure the expression levels of different osteoblastogenic proteins in vascular smooth muscle cells obtained from different treatment groups.

Results: The serum CTRP3 levels were significantly lower in patients with CAC than in those without CAC, and even lower in patients with both CAC and diabetes mellitus. CTRP3 played roles as a protective factor and potential predictor in CAC. CTRP3 inhibited the osteogenic differentiation of vascular smooth muscle cells induced under high glucose and lipid conditions by inhibiting the nuclear translocation of β-catenin.

Conclusions: CTRP3 may serve as a valuable screening biomarker and a novel therapeutic target in CAC, particularly in diabetes patients.

Keywords: Adipokine; Biomarker; Coronary heart disease; Coronary vessels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Case-Control Studies
  • Coronary Vessels / pathology
  • Humans
  • Mice
  • Muscle, Smooth, Vascular / metabolism
  • Osteogenesis*
  • Vascular Calcification* / etiology
  • Vascular Calcification* / prevention & control
  • beta Catenin / metabolism

Substances

  • Biomarkers
  • beta Catenin