Intrinsic pathway-mediated apoptosis in elastase-induced aneurysms in rabbits

Ramanathan D Kadirvel, Y. H. Ding, D. Dai, D. A. Lewis, David F Kallmes

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Abstract

BACKGROUND AND OBJECTIVES: The pathophysiology of saccular aneurysms is complex and multi-factorial. 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.

Original languageEnglish (US)
Pages (from-to)165-169
Number of pages5
JournalAmerican Journal of Neuroradiology
Volume31
Issue number1
DOIs
StatePublished - Jan 2010

Fingerprint

Pancreatic Elastase
Aneurysm
Apoptosis
Rabbits
Caspase 9
Common Carotid Artery
In Situ Nick-End Labeling
Proteins
Caspase 2
Death Domain Receptors
DNA Nucleotidylexotransferase
Caspase 8
Caspase 3
Western Blotting
Staining and Labeling

ASJC Scopus subject areas

  • Clinical Neurology
  • Radiology Nuclear Medicine and imaging

Cite this

Intrinsic pathway-mediated apoptosis in elastase-induced aneurysms in rabbits. / Kadirvel, Ramanathan D; Ding, Y. H.; Dai, D.; Lewis, D. A.; Kallmes, David F.

In: American Journal of Neuroradiology, Vol. 31, No. 1, 01.2010, p. 165-169.

Research output: Contribution to journalArticle

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