Document Detail


Molecular indices of apoptosis activation in elastase-induced aneurysms after embolization with platinum coils.
MedLine Citation:
PMID:  17717314     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Even though endovascular coils have been widely used for the treatment of intracranial aneurysms, the cellular and molecular responses of aneurysms to the coils after embolization remain poorly understood. The aim of the present study was to understand the mechanism of apoptosis in aneurysms embolized with platinum coils in the rabbit model of elastase-induced aneurysms. METHODS: Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery in 30 rabbits. Aneurysms were allowed to mature for 8 weeks, after which 20 aneurysms were embolized with platinum coils by endovascular means. After 2 (n=10) and 4 (n=10) weeks of implantation, aneurysm samples harboring coils were harvested for apoptotic studies. The remaining 10 uncoiled aneurysms were used as controls; additional controls included the left common carotid artery, which had not undergone any surgical procedure. Control samples were harvested at 12 weeks after aneurysm creation. RESULTS: Expression of procaspases-3, -8, and -9 was elevated in coiled aneurysms embolized with platinum coils at both time points when compared with uncoiled aneurysms and the left common carotid artery. Cleaved caspases-3, -8, and -9 were found to be expressed only at 4 weeks after embolization. Cells within the aneurysm cavity were terminal dUTP nick end-labeling-positive at 4 weeks only. These apoptotic cells were identified as smooth muscle actin-positive cells. Expression of tumor necrosis-alpha was high in coiled aneurysms when compared with controls. There was no significant difference in the expression of Fas ligand among groups. Decreased expression of antiapoptotic proteins Bcl-2 and phospho-Bad, as well as increased expression of proapoptotic proteins Bax and Bid, was observed in coiled aneurysms at both time points. CONCLUSIONS: Activation of apoptosis in aneurysms after embolization with platinum coils is induced by both tumor necrosis factor-alpha-mediated extrinsic and Bcl-2-mediated intrinsic pathways.
Authors:
Ramanathan Kadirvel; Yong-Hong Ding; Daying Dai; Debra A Lewis; Harry J Cloft; David 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:  2007-08-23
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  38     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-25     Completed Date:  2007-10-18     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2787-94     Citation Subset:  IM    
Affiliation:
Department of Radiology, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / physiology*
Carotid Artery, Common / pathology
Caspase 3 / metabolism
Caspase 8 / metabolism
Caspase 9 / metabolism
Disease Models, Animal
Embolization, Therapeutic / instrumentation,  methods*
Fibroblasts / metabolism,  pathology
In Situ Nick-End Labeling
Intracranial Aneurysm / metabolism,  pathology*,  therapy*
Pancreatic Elastase
Platinum*
Proto-Oncogene Proteins c-bcl-2 / metabolism
Rabbits
Tumor Necrosis Factor-alpha / metabolism
Grant Support
ID/Acronym/Agency:
2R01NS042646-04/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Necrosis Factor-alpha; 7440-06-4/Platinum; EC 3.4.21.36/Pancreatic Elastase; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspase 9

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


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