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A novel promising therapy for vein graft restenosis: Overexpressed Nogo-B induces vascular smooth muscle cell apoptosis by activation of the JNK/p38 MAPK signaling pathway.
MedLine Citation:
PMID:  21612877     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Coronary artery bypass grafting using autologous saphenous veins is a standard surgical therapy for coronary artery diseases. However, post-procedure vein graft restenosis impedes its effectiveness and often leads to a high morbidity and mortality, and a reduction in the quality of life. Neointimal hyperplasia is a major cause of vein graft occlusion, and is characterized by an imbalance between vascular smooth muscle cell (VSMC) proliferation and apoptosis. So far, there have been no optimally effective pharmacological or non-pharmacological interventions for the prevention and treatment of vein graft occlusion. Gene therapy has emerged as a potential therapeutic approach, as bypass grafts can be genetically modified ex vivo prior to grafting in the coronary vasculature. Nogo-B, recognized as a vascular protective factor, has been shown to reduce neointimal thickening in graft veins, but its specific mechanism is uncertain. Evidence from diverse sources has documented that overexpressed Nogo-B can induce apoptosis of variant cancer cell lines, suggesting that overexpressed Nogo-B may have a pro-apoptotic role in VSMC. Furthermore, we have found that Nogo-B is associated with the mitogen-activated protein kinase (MAPK) signaling pathway, which plays important roles in cell growth, differentiation, and apoptosis. Recent studies have shown that VSMC apoptosis can be induced by activation of the c-Jun-N-terminal kinase (JNK)/p38 MAPK pathway. Therefore, we propose that overproduction of Nogo-B in the graft vein could result in reduced neointimal hyperplasia, the mechanism of which involves increased VSMC apoptosis induced by activation of the JNK/p38 MAPK pathway. This study will provide a new clue for gene therapy in the treatment of vein graft failure.
Authors:
Hui Zheng; Song Xue; Feng Lian; Yong-Yi Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-23
Journal Detail:
Title:  Medical hypotheses     Volume:  -     ISSN:  1532-2777     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7505668     Medline TA:  Med Hypotheses     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
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