Document Detail

Altered oxidative stress responses and increased type I collagen expression in bicuspid aortic valve patients.
MedLine Citation:
PMID:  21095332     Owner:  NLM     Status:  MEDLINE    
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.
Julie A Phillippi; Michael A Eskay; Adam A Kubala; Bruce R Pitt; Thomas G Gleason
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  90     ISSN:  1552-6259     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-01-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1893-8     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Department of Cardiothoracic Surgery, Center for Thoracic Aortic Disease, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
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MeSH Terms
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
Mice, Inbred C57BL
Middle Aged
Muscle, Smooth, Vascular / metabolism,  pathology
Oxidative Stress / drug effects,  physiology*
RNA / biosynthesis,  genetics*
Reactive Oxygen Species / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Vascular Endothelial Growth Factor A / pharmacology
Reg. No./Substance:
0/Collagen Type I; 0/Reactive Oxygen Species; 0/Vascular Endothelial Growth Factor A; 63231-63-0/RNA

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