Related Experiment Video

Updated: Aug 23, 2025

Murine Model of Thoracic Aortic Dissection Induced by Oral β-Aminopropionitrile and Subcutaneous Angiotensin II Infusion
05:31

Murine Model of Thoracic Aortic Dissection Induced by Oral β-Aminopropionitrile and Subcutaneous Angiotensin II Infusion

Published on: May 16, 2025

260

11S Proteasome Activator REGγ Promotes Aortic Dissection by Inhibiting RBM3 (RNA Binding Motif Protein 3) Pathway

Yifan Xie1,2,3, Rifeng Gao1,2, Yang Gao1,2

  • 1Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China (Y.X., R.G., Y.G., Z.D., J.G.).

Hypertension (Dallas, Tex. : 1979)
|November 4, 2022
PubMed
Abstract

Insights

Proteasome activator REGγ promotes aortic dissection (AD) by degrading RBM3, which normally stabilizes contractile VSMC genes. Inhibiting REGγ may offer a new therapeutic strategy for AD-associated cardiovascular dysfunction.

Area of Science:

  • Cardiovascular Biology
  • Proteasome Regulation
  • Vascular Smooth Muscle Cell Biology

Background:

  • Aortic dissection (AD) is a life-threatening cardiovascular condition with high mortality and poorly understood mechanisms.
  • REGγ, an 11S proteasome activator, is identified as a novel regulator in the cardiovascular system.
  • REGγ degrades proteins independently of ubiquitination and ATP, suggesting a unique role in cellular regulation.

Purpose of the Study:

  • To investigate the role of REGγ in the progression of aortic dissection (AD).
  • To elucidate the molecular mechanisms by which REGγ influences vascular smooth muscle cell (VSMC) phenotype.
  • To explore the therapeutic potential of targeting REGγ for AD treatment.

Main Methods:

  • Utilized a β-aminopropionitrile (BAPN)-induced mouse model of AD with REGγ knockout.
  • Employed angiotensin II (Ang II)-treated REGγ-deficient VSMCs in vitro.
  • Investigated the interaction between REGγ, RBM3, and SRF, and their impact on VSMC-specific genes.

Main Results:

  • REGγ expression was upregulated in AD models (in vivo and in vitro).
  • REGγ deficiency ameliorated AD progression by preventing VSMC phenotypic switching via suppression of RBM3 decay.
  • REGγ directly degraded RBM3, leading to reduced SRF activity and decreased expression of contractile markers (α-SMA, SM22α), promoting the synthetic VSMC phenotype and AD progression.

Conclusions:

  • REGγ promotes VSMC phenotypic switching and AD progression by inhibiting the RBM3-SRF pathway.
  • Targeting REGγ-proteasome activity presents a potential therapeutic avenue for AD-associated cardiovascular dysfunction.
Keywords:
aminopropionitrileangiotensin IIcardiovascular diseasesproteasome

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