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A Human Ex Vivo Atherosclerotic Plaque Model to Study Lesion Biology
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Nucleotide-binding oligomerization domain protein 2 deficiency enhances CHOP expression and plaque necrosis in

Min-Young Kwon1,2, Narae Hwang1, Sung Hoon Back1

  • 1Laboratory of Molecular Immunology, Department of Biological Sciences, University of Ulsan, South Korea.

The FEBS Journal
|March 14, 2020
PubMed

Insights

Nucleotide-binding oligomerization domain protein 2 (NOD2) protects against endoplasmic reticulum (ER) stress-induced cell death in vascular smooth muscle cells (VSMCs). NOD2 deficiency exacerbates atherosclerotic plaque instability and CHOP expression.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cell Biology
  • Immunology

Background:

  • Endoplasmic reticulum (ER) stress contributes to vascular smooth muscle cell (VSMC) death and atherosclerotic plaque stabilization.
  • Nucleotide-binding oligomerization domain protein 2 (NOD2) is implicated in vascular homeostasis and injury, but its role in ER stress-induced VSMC death is unclear.

Purpose of the Study:

  • To investigate the role and mechanisms of NOD2 in ER stress-induced VSMC death during vascular diseases, particularly advanced atherosclerosis.

Main Methods:

  • Investigated NOD2 interaction with ER stress sensor ATF6.
  • Assessed CHOP expression in NOD2-deficient mice after femoral artery injury.
  • Evaluated the effect of NOD2 ligand MDP and NOD2 overexpression on CHOP expression in VSMCs.
  • Examined atherosclerotic lesions in NOD2-/- ApoE-/- mice.

Main Results:

  • NOD2 directly interacted with ATF6, suppressing the expression of the proapoptotic factor CHOP during ER stress.
  • NOD2 deficiency led to increased CHOP-positive cells in neointimal lesions and promoted atherosclerotic lesion disruption.
  • NOD2 ligand MDP and NOD2 overexpression reduced CHOP expression in wild-type VSMCs.

Conclusions:

  • NOD2 acts as a negative regulator of ER stress-induced apoptosis in VSMCs by inhibiting ATF6 activation and CHOP expression.
  • NOD2 plays a critical role in stabilizing atherosclerotic plaques by mitigating ER stress-induced VSMC death.
Keywords:
ATF6CHOPER stressNOD2cell death

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