Article ; Online: Novel role of peptidoglycan recognition protein 2 in activating NOD2-NFκB inflammatory axis in coronary artery disease.
2023 Volume 389, Page(s) 117436
Abstract: Backgrounds and aims: The role of inflammation in driving atherosclerosis is well-established. It exerts systemic effects beyond the local site of plaque formation. In the context of coronary artery disease (CAD), the proteins that show altered levels ... ...
| Abstract | Backgrounds and aims: The role of inflammation in driving atherosclerosis is well-established. It exerts systemic effects beyond the local site of plaque formation. In the context of coronary artery disease (CAD), the proteins that show altered levels in the plasma, are potentially important for understanding the key regulatory mechanism in the pathogenesis of atherosclerosis. A case-control study revealed that plasma soluble Peptidoglycan Recognition Protein 2 (PGLYRP2) primarily produced by the liver, is increased in subjects with CAD. Furthermore, the concentration of PGLYRP2 in the blood correlates with the severity of coronary artery disease. Thus, it raises interest in understanding the exact role of the protein in aortic inflammation and plaque progression. Methods: We evaluated the plasma concentration of PGLYRP2 in three distinct groups: patients with CAD (N = 68), asymptomatic individuals (N = 34), and healthy volunteers (N = 20). Furthermore, we investigated the correlation between disease severity and PGLYRP2 levels in CAD patients. To identify potential binding partners of PGLYRP2, we employed computational analysis. We verified the PGLYRP2-NOD2 interaction in macrophage cells and elucidated the inflammatory pathways activated by PGLYRP2 within these cells. To assess the impact of PGLYRP2, we examined its effects in the atherosclerotic mice model (ApoE Results: In this study, we report for the first time that Nucleotide-binding Oligomerization domain 2 (NOD2) which is expressed on the surface of macrophages, is a receptor of PGLYRP2. The N-terminal domain of PGLYRP2 directly binds to NOD2 and activates the NOD2-RIP2-NFκB cascade that promotes the secretion of proinflammatory cytokines like TNFα, IL1β, and IL-8. In the atherosclerotic mice model (ApoE Conclusions: Taken together, our data demonstrate that NOD2 acts as a receptor of PGLYRP2 on macrophages, which mediates the activation of the NOD2-RIP2-NFκB pathway and promotes inflammation, thus significantly contributing to the development and progression of atherosclerosis. |
|---|---|
| MeSH term(s) | Animals ; Humans ; Mice ; Apolipoproteins E/metabolism ; Atherosclerosis/pathology ; Carrier Proteins/metabolism ; Case-Control Studies ; Coronary Artery Disease ; Cytokines/metabolism ; Inflammation/metabolism ; Nod2 Signaling Adaptor Protein/genetics ; Nod2 Signaling Adaptor Protein/metabolism ; N-Acetylmuramoyl-L-alanine Amidase/metabolism |
| Chemical Substances | Apolipoproteins E ; Carrier Proteins ; Cytokines ; NOD2 protein, human ; Nod2 Signaling Adaptor Protein ; peptidoglycan recognition protein ; Pglyrp2 protein, mouse (EC 3.5.1.28) ; N-Acetylmuramoyl-L-alanine Amidase (EC 3.5.1.28) |
| Language | English |
| Publishing date | 2023-12-27 |
| Publishing country | Ireland |
| Document type | Journal Article |
| ZDB-ID | 80061-2 |
| ISSN | 1879-1484 ; 0021-9150 |
| ISSN (online) | 1879-1484 |
| ISSN | 0021-9150 |
| DOI | 10.1016/j.atherosclerosis.2023.117436 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 226: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.