Cholinergic anti-inflammatory pathway inhibits neointimal hyperplasia by suppressing inflammation and oxidative stress
| Autor: | Fu-Ming Shen, Yong-Hua Li, Hui Fu, Le-Feng Qu, Pei Wang, Dong-Jie Li, Jie Tong |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
WT wild type Vascular smooth muscle alpha7 Nicotinic Acetylcholine Receptor GSH reduced glutathione Clinical Biochemistry MPO myeloperoxidase Constriction Pathologic medicine.disease_cause Biochemistry TNF-α tumor necrosis factor-α Muscle Smooth Vascular CCL2 chemokines chemokine (C-C motif) ligand 2 Cell Movement Cholinergic anti-inflammatory pathway 3-NT 3-nitrotyrosine lcsh:QH301-705.5 Neointimal hyperplasia Mice Knockout lcsh:R5-920 biology Chemistry CXCL2 chemokine (CXC motif) ligand 2 CAP cholinergic anti-inflammatory pathway NADPH Oxidase 4 Benzamides NADPH Oxidase 2 NADPH Oxidase 1 cardiovascular system Tumor necrosis factor alpha Stents medicine.symptom lcsh:Medicine (General) VSMCs vascular smooth muscle cells Research Paper Neointima α7 nicotinic acetylcholine receptor medicine.medical_specialty IL-1β interleukin-1β Inflammation CNS central nervous system α-SMA α-smooth muscle actin Superoxide dismutase 03 medical and health sciences Bridged Bicyclo Compounds Internal medicine SOD superoxide dismutase medicine Animals Humans Cell Proliferation MDA malondialdehyde KO knockout Hyperplasia Organic Chemistry α7nAChR α7 nicotinic acetylcholine receptor medicine.disease 030104 developmental biology Endocrinology Gene Expression Regulation lcsh:Biology (General) Oxidative stress Immunology biology.protein |
| Zdroj: | Redox Biology, Vol 15, Iss C, Pp 22-33 (2018) Redox Biology |
| ISSN: | 2213-2317 |
| Popis: | Neointimal hyperplasia as a consequence of vascular injury is aggravated by inflammatory reaction and oxidative stress. The α7 nicotinic acetylcholine receptor (α7nAChR) is a orchestrator of cholinergic anti-inflammatory pathway (CAP), which refers to a physiological neuro-immune mechanism that restricts inflammation. Here, we investigated the potential role of CAP in neointimal hyperplasia using α7nAChR knockout (KO) mice. Male α7nAChR-KO mice and their wild-type control mice (WT) were subjected to wire injury in left common carotid artery. At 4 weeks post injury, the injured aortae were isolated for examination. The neointimal hyperplasia after wire injury was significantly aggravated in α7nAChR-KO mice compared with WT mice. The α7nAChR-KO mice had increased collagen contents and vascular smooth muscle cells (VSMCs) amount. Moreover, the inflammation was significantly enhanced in the neointima of α7nAChR-KO mice relative to WT mice, evidenced by the increased expression of tumor necrosis factor-α/interleukin-1β, and macrophage infiltration. Meanwhile, the chemokines chemokine (C-C motif) ligand 2 and chemokine (CXC motif) ligand 2 expression was also augmented in the neointima of α7nAChR-KO mice compared with WT mice. Additionally, the depletion of superoxide dismutase (SOD) and reduced glutathione (GSH), and the upregulation of 3-nitrotyrosine, malondialdehyde and myeloperoxidase were more pronounced in neointima of α7nAChR-KO mice compared with WT mice. Accordingly, the protein expression of NADPH oxidase 1 (Nox1), Nox2 and Nox4, was also higher in neointima of α7nAChR-KO mice compared with WT mice. Finally, pharmacologically activation of CAP with a selective α7nAChR agonist PNU-282987, significantly reduced neointima formation, arterial inflammation and oxidative stress after vascular injury in C57BL/6 mice. In conclusion, our results demonstrate that α7nAChR-mediated CAP is a neuro-physiological mechanism that inhibits neointima formation after vascular injury via suppressing arterial inflammation and oxidative stress. Further, these results imply that targeting α7nAChR may be a promising interventional strategy for in-stent stenosis. |
| Databáze: | OpenAIRE |
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