title: Zinc Prevents Abdominal Aortic Aneurysm Formation by Induction of A20-Mediated Suppression of NF-κB Pathway.
abstract: Chronic inflammation and degradation of elastin are the main processes in the development of abdominal aortic aneurysm (AAA). Recent studies show that zinc has an anti-inflammatory effect. Based on these, zinc may render effective therapy for the treatment of the AAA. Currently, we want to investigate the effects of zinc on AAA progression and its related molecular mechanism. Rat AAA models were induced by periaortic application of CaCl2. AAA rats were treated by daily intraperitoneal injection of ZnSO4 or vehicle alone. The aorta segments were collected at 4 weeks after surgery. The primary rat aortic vascular smooth muscle cells (VSMCs) were stimulated with TNF-α alone or with ZnSO4 for 3 weeks. The results showed that zinc supplementation significantly suppressed the CaCl2-induced expansion of the abdominal aortic diameter, as well as a preservation of medial elastin fibers in the aortas. Zinc supplementation also obviously attenuated infiltration of the macrophages and lymphocytes in the aortas. In addition, zinc reduced MMP-2 and MMP-9 production in the aortas. Most importantly, zinc treatment significantly induced A20 expression, along with inhibition of the NF-κB canonical signaling pathway in vitro in VSMCs and in vivo in rat AAA. This study demonstrated, for the first time, that zinc supplementation could prevent the development of rat experimental AAA by induction of A20-mediated inhibition of the NF-κB canonical signaling pathway.
authors.affiliation: Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, China.
authors.forename: Ya-Wei
authors.initials: YW
authors.lastname: Yan
authors.affiliation: Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, China.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Bai
authors.affiliation: Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, China.
authors.forename: Wei-Jian
authors.initials: WJ
authors.lastname: Hou
authors.affiliation: Department of Cell Biology, College of Basic Medicine, China Medical University, Shenyang, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Tong
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D019287:Zinc Sulfate / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D000072000:NF-KappaB Inhibitor alpha; D019287:Zinc Sulfate; D004549:Elastin; D051550:I-kappa B Kinase; C000602677:TNFAIP3 protein, rat; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat