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Updated: Sep 16, 2025

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Smooth muscle-specific HuR knockout attenuates vascular calcification.

Ang Chen1, Peidong Yuan1, Yue Lu1

  • 1State Key Laboratory for Innovation and Transformation of Luobing Theory; Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province; Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, China.

Journal of Molecular and Cellular Cardiology
|July 6, 2025
PubMed
Summary

Human antigen R (HuR) promotes vascular calcification by stabilizing Runt-related transcription factor 2 (Runx2) mRNA. Inhibiting HuR or its smooth muscle-specific knockout protects against this condition.

Keywords:
HuRRunx2Vascular calcificationVascular smooth muscle cells

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Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Vascular Biology

Background:

  • Vascular calcification is a prevalent pathological feature in atherosclerosis, chronic kidney disease, and aging.
  • Human antigen R (HuR), an RNA-binding protein, is implicated in various diseases, but its role in vascular calcification is not well understood.

Purpose of the Study:

  • To investigate the function of HuR in vascular calcification.
  • To elucidate the molecular mechanisms by which HuR regulates vascular calcification.

Main Methods:

  • Generation of smooth muscle-specific HuR knockout (HuRSMKO) mice.
  • Assessment of vascular calcification in vitro using vascular smooth muscle cells (VSMCs) and in vivo in mice.
  • Analysis of HuR expression regulation by high phosphate via ATF4.
  • Investigation of HuR's interaction with Runx2 mRNA.

Main Results:

  • HuR expression is upregulated under calcifying conditions, induced by high phosphate via ATF4.
  • HuR overexpression exacerbates high phosphate-induced VSMC calcification, while HuR deficiency inhibits it.
  • Smooth muscle-specific knockout of HuR and treatment with a HuR inhibitor (CMLD-2) attenuated vascular calcification in vivo.
  • HuR directly binds to Runx2 mRNA, enhancing its stability and protein expression.

Conclusions:

  • HuR plays a critical role in regulating vascular calcification.
  • HuR facilitates vascular calcification through posttranscriptional control of Runx2.
  • Targeting HuR represents a potential therapeutic strategy for vascular calcification.