Document Detail


Intrinsic pathway-mediated apoptosis in elastase-induced aneurysms in rabbits.
MedLine Citation:
PMID:  19749227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND OBJECTIVES: The pathophysiology of saccular aneurysms is complex and multifactorial. The aim of the present study was to understand the mechanism of apoptosis in an elastase-induced aneurysm model in rabbits.
MATERIALS AND METHODS: Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery in 20 rabbits. Aneurysm samples were harvested at 2 and 12 weeks after creation. Expression of apoptosis-associated proteins, including caspases and bcl-2 proteins, were assessed by Western blot analysis (n = 5 at both time points). Terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) staining, which indicates the presence of apoptosis, was performed in tissue sections (n = 5 at both time points). The unoperated contralateral common carotid artery was used as a control.
RESULTS: Expression of active caspase-3, the final executioner of apoptosis, and caspase-9, the mediator of the intrinsic mitochondrial pathway, was observed in aneurysms at 2 weeks, whereas the expression of activated caspase-8, the mediator of the extrinsic death receptor pathway, was absent at both time points. Expression of antiapoptotic proteins, Bcl-2 and phospho-Bad, was down-regulated in aneurysms compared with controls at 2 weeks. None of these proteins were differentially expressed at 12 weeks. These results were confirmed by the presence of TUNEL-positive cells in some aneurysms at the early time point.
CONCLUSIONS: In this study of elastase-induced aneurysms in a rabbit model, activation of apoptosis is mediated predominantly by the Bcl-2-mediated intrinsic pathway through the activation of caspase-9.
Authors:
R Kadirvel; Y H Ding; D Dai; D A Lewis; D F Kallmes
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-09-12
Journal Detail:
Title:  AJNR. American journal of neuroradiology     Volume:  31     ISSN:  1936-959X     ISO Abbreviation:  AJNR Am J Neuroradiol     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-15     Completed Date:  2010-03-19     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  8003708     Medline TA:  AJNR Am J Neuroradiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  165-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Intracranial Aneurysm / chemically induced,  physiopathology*
Pancreatic Elastase / administration & dosage
Rabbits
Grant Support
ID/Acronym/Agency:
2R01NS042646-04/NS/NINDS NIH HHS; R01 NS042646/NS/NINDS NIH HHS; R01 NS042646-07/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
EC 3.4.21.36/Pancreatic Elastase
Comments/Corrections

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