| First Author | Kwon MY | Year | 2020 |
| Journal | FEBS J | Volume | 287 |
| Issue | 10 | Pages | 2055-2069 |
| PubMed ID | 32167239 | Mgi Jnum | J:306913 |
| Mgi Id | MGI:6705377 | Doi | 10.1111/febs.15294 |
| Citation | Kwon MY, et al. (2020) Nucleotide-binding oligomerization domain protein 2 deficiency enhances CHOP expression and plaque necrosis in advanced atherosclerotic lesions. FEBS J 287(10):2055-2069 |
| abstractText | Endoplasmic reticulum (ER) stress-induced cell death of vascular smooth muscle cells (VSMCs) is extensively involved in atherosclerotic plaque stabilization. We previously reported that nucleotide-binding oligomerization domain protein 2 (NOD2) participated in vascular homeostasis and tissue injury. However, the role and underlying mechanisms of NOD2 remain unknown in ER stress-induced cell death of VSMC during vascular diseases, including advanced atherosclerosis. Here, we report that NOD2 specifically interacted with ER stress sensor activating transcription factor 6 (ATF6) and suppressed the expression of proapoptotic transcription factor CHOP (C/EBP homologous protein) during ER stress. CHOP-positive cells were increased in neointimal lesions after femoral artery injury in NOD2-deficient mice. In particular, a NOD2 ligand, MDP, and overexpression of NOD2 decreased CHOP expression in wild-type VSMCs. NOD2 interacted with an ER stress sensor molecule, ATF6, and acted as a negative regulator for ATF6 activation and its downstream target molecule, CHOP, that regulates ER stress-induced apoptosis. Moreover, NOD2 deficiency promoted disruption of advanced atherosclerotic lesions and CHOP expression in NOD2(-/-) ApoE(-/-) mice. Our findings indicate an unsuspected critical role for NOD2 in ER stress-induced cell death. |
