IL-12Rβ2 is Expressed in the Synthetic SMC and Detected in the Blood of Patients With Acute Myocardial Infarction

Dong Hoon Kang1, Hee Su Lee1, Jin-Ah Yang2

  • 1Department of Life Science, Ewha Womans University, Seoul, Korea.

Abstract

Insights

Interleukin-12 receptor beta 2 subunit (IL-12Rβ2) is elevated in atherosclerosis and released in extracellular vesicles in acute myocardial infarction patients. This offers a new biomarker for vulnerable plaques.

Area of Science:

  • Cardiovascular Biology
  • Biomarker Discovery
  • Atherosclerosis Research

Background:

  • Smooth muscle cell (SMC) de-differentiation and proliferation drive vascular remodeling in atherosclerosis.
  • Current biomarkers do not adequately reflect SMC phenotypic changes associated with vulnerable plaques.

Purpose of the Study:

  • To investigate the role of Interleukin-12 receptor beta 2 subunit (IL-12Rβ2) in SMCs and its potential as a biomarker for vulnerable atherosclerotic plaques.
  • To develop a method for detecting circulating IL-12Rβ2.

Main Methods:

  • Quantitative real-time PCR, immunoblotting, flow cytometry, and immunohistochemistry were used to characterize IL-12Rβ2 expression in human SMCs and atherosclerotic arteries.
  • siRNA-mediated knockdown of IL-12Rβ2 was performed in vitro and in a rat carotid balloon injury model.
  • A capture ELISA was developed to measure plasma IL-12Rβ2 levels.

Main Results:

  • IL-12Rβ2 protein expression was significantly higher in atherosclerotic carotid arteries compared to normal arteries.
  • Interferon-gamma (IFN-γ) induced IL-12Rβ2 expression in synthetic SMCs.
  • IL-12Rβ2 knockdown reduced SMC proliferation, migration, and monocyte adhesion, and inhibited neointimal thickening in vivo.
  • Circulating IL-12Rβ2 was detected in extracellular vesicles (EVs) from acute myocardial infarction (AMI) patients and quantified via ELISA.

Conclusions:

  • IL-12Rβ2 is selectively induced in synthetic SMCs by IFN-γ and released into circulation via EVs in AMI patients.
  • IL-12Rβ2 represents a novel biomarker for detecting vulnerable atherosclerotic plaques.
  • A newly developed ELISA system enables the quantification of circulating IL-12Rβ2.

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