Document Detail


Vanin-1 pantetheinase drives smooth muscle cell activation in post-arterial injury neointimal hyperplasia.
MedLine Citation:
PMID:  22720042     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pantetheinase vanin-1 generates cysteamine, which inhibits reduced glutathione (GSH) synthesis. Vanin-1 promotes inflammation and tissue injury partly by inducing oxidative stress, and partly by peroxisome proliferator-activated receptor gamma (PPARγ) expression. Vascular smooth muscle cells (SMCs) contribute to neointimal hyperplasia in response to injury, by multiple mechanisms including modulation of oxidative stress and PPARγ. Therefore, we tested the hypothesis that vanin-1 drives SMC activation and neointimal hyperplasia. We studied reactive oxygen species (ROS) generation and functional responses to platelet-derived growth factor (PDGF) and the pro-oxidant diamide in cultured mouse aortic SMCs, and also assessed neointima formation after carotid artery ligation in vanin-1 deficiency. Vnn1(-/-) SMCs demonstrated decreased oxidative stress, proliferation, migration, and matrix metalloproteinase 9 (MMP-9) activity in response to PDGF and/or diamide, with the effects on proliferation linked, in these studies, to both increased GSH levels and PPARγ expression. Vnn1(-/-) mice displayed markedly decreased neointima formation in response to carotid artery ligation, including decreased intima:media ratio and cross-sectional area of the neointima. We conclude that vanin-1, via dual modulation of GSH and PPARγ, critically regulates the activation of cultured SMCs and development of neointimal hyperplasia in response to carotid artery ligation. Vanin-1 is a novel potential therapeutic target for neointimal hyperplasia following revascularization.
Authors:
K Jagadeesha Dammanahalli; Stephanie Stevens; Robert Terkeltaub
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-06-13
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-21     Completed Date:  2012-12-13     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e39106     Citation Subset:  IM    
Affiliation:
San Diego VA Healthcare System and Department of Medicine, University of California San Diego, San Diego, California, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Amidohydrolases / genetics,  metabolism,  physiology*
Animals
Arteries / injuries*
Base Sequence
Blotting, Western
DNA Primers
Electrophoresis, Polyacrylamide Gel
GPI-Linked Proteins / genetics,  metabolism,  physiology
Hyperplasia
Mice
Mice, Knockout
Muscle, Smooth / cytology,  metabolism,  physiology*
Oxidative Stress
Reactive Oxygen Species / metabolism
Real-Time Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
HL077360/HL/NHLBI NIH HHS; HL087252/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/GPI-Linked Proteins; 0/Reactive Oxygen Species; EC 3.5.-/Amidohydrolases; EC 3.5.1.-/pantetheinase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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