title: Deletion of metallothionein exacerbates intermittent hypoxia-induced oxidative and inflammatory injury in aorta.
abstract: The present study was to explore the effect of metallothionein (MT) on intermittent hypoxia (IH) induced aortic pathogenic changes. Markers of oxidative damages, inflammation, and vascular remodeling were observed by immunohistochemical staining after 3 days and 1, 3, and 8 weeks after IH exposures. Endogenous MT was induced after 3 days of IH but was significantly decreased after 8 weeks of IH. Compared with the wild-type mice, MT knock-out mice exhibited earlier and more severe pathogenic changes of oxidative damages, inflammatory responses, and cellular apoptosis, as indicated by the significant accumulation of collagen, increased levels of connective tissue growth factor, transforming growth factor β1, tumor necrosis factor-alpha, vascular cell adhesion molecule 1,3-nitrotyrosine, and 4-hydroxy-2-nonenal in the aorta. These findings suggested that chronic IH may lead to aortic damages characterized by oxidative stress and inflammation, and MT may play a pivotal role in the above pathogenesis process.
authors.affiliation: The Center of Cardiovascular Diseases at the First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, China ; Kosair Children's Hospital Research Institute at the Department of Pediatrics, University of Louisville, 570 South Preston Street, Baxter I, Suite 321B, Louisville, KY 40202, USA.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhou
authors.affiliation: The Center of Cardiovascular Diseases at the First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, China ; Kosair Children's Hospital Research Institute at the Department of Pediatrics, University of Louisville, 570 South Preston Street, Baxter I, Suite 321B, Louisville, KY 40202, USA.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Kosair Children's Hospital Research Institute at the Department of Pediatrics, University of Louisville, 570 South Preston Street, Baxter I, Suite 321B, Louisville, KY 40202, USA ; Chinese-American Research Institute for Diabetic Complication, Wenzhou Medical College, Wenzhou 325035, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Cai
authors.affiliation: Kosair Children's Hospital Research Institute at the Department of Pediatrics, University of Louisville, 570 South Preston Street, Baxter I, Suite 321B, Louisville, KY 40202, USA ; Departments of Radiation Oncology and Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.affiliation: Kosair Children's Hospital Research Institute at the Department of Pediatrics, University of Louisville, 570 South Preston Street, Baxter I, Suite 321B, Louisville, KY 40202, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: The Center of Cardiovascular Diseases at the First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia; D008668:Metallothionein / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000447:Aldehydes; C526318:CCN2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D055513:Connective Tissue Growth Factor; C002744:3-nitrotyrosine; D014443:Tyrosine; D008668:Metallothionein; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; C027576:4-hydroxy-2-nonenal