| Altered oxidative stress responses and increased type I collagen expression in bicuspid aortic valve patients. | |
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MedLine Citation:
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PMID: 21095332 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The mechanisms governing extracellular matrix degradation and smooth muscle cell (SMC) loss in the ascending aorta of bicuspid aortic valve (BAV) patients are unknown. We recently reported that expression and induction of metallothionein, a reactive oxygen species scavenger, is reduced in BAV ascending aortic aneurysms relative to nonaneurysmal patients. METHODS: Tissue and primary SMCs from patients with and without thoracic aortic aneurysms and metallothionein-null and wild-type mice were analyzed for cell viability, vascular endothelial growth factor (VEGF), and type I collagen gene expression during exposure to reactive oxygen species. RESULTS: The BAV SMCs and metallothionein -/- mice failed to induce VEGF under conditions of oxidative stress in vitro. Exogenous VEGF restored resistance to oxidative stress in BAV SMCs to normal. Type I collagen gene induction was increased in BAV aorta. CONCLUSIONS: Lack of VEGF induction during exposure to reactive oxygen species suggest that the oxidative stress response is faulty upstream of metallothionein and VEGF in BAV SMCs. Improvement of cell viability with VEGF treatment suggests that the deficient pathway can be rescued by VEGF. Increased type I collagen in BAV suggests that lack of metallothionein/VEGF activation in response to reactive oxygen species may play a role in extracellular matrix homeostasis of the ascending aorta. These data continue to support our hypothesis that BAV SMCs lack sufficient resistance to reactive oxygen species to maintain extracellular matrix homeostasis, which imparts a predisposition to thoracic aortic aneurysms. |
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Authors:
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Julie A Phillippi; Michael A Eskay; Adam A Kubala; Bruce R Pitt; Thomas G Gleason |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Annals of thoracic surgery Volume: 90 ISSN: 1552-6259 ISO Abbreviation: Ann. Thorac. Surg. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-24 Completed Date: 2011-01-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 15030100R Medline TA: Ann Thorac Surg Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1893-8 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Cardiothoracic Surgery, Center for Thoracic Aortic Disease, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Animals Aortic Valve / abnormalities, metabolism* Collagen Type I / biosynthesis, genetics* Disease Models, Animal Gene Expression Regulation* Genetic Predisposition to Disease* Heart Valve Diseases / congenital, genetics*, metabolism Humans Mice Mice, Inbred C57BL Middle Aged Muscle, Smooth, Vascular / metabolism, pathology Oxidative Stress / drug effects, physiology* Prognosis RNA / biosynthesis, genetics* Reactive Oxygen Species / metabolism Reverse Transcriptase Polymerase Chain Reaction Vascular Endothelial Growth Factor A / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Collagen Type I; 0/Reactive Oxygen Species; 0/Vascular Endothelial Growth Factor A; 63231-63-0/RNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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