PT  - JOURNAL ARTICLE
AU  - R. Kadirvel
AU  - Y.H. Ding
AU  - D. Dai
AU  - D.A. Lewis
AU  - D.F. Kallmes
TI  - Intrinsic Pathway−Mediated Apoptosis in Elastase-Induced Aneurysms in Rabbits
AID  - 10.3174/ajnr.A1781
DP  - 2010 Jan 01
TA  - American Journal of Neuroradiology
PG  - 165--169
VI  - 31
IP  - 1
4099  - http://www.ajnr.org/content/31/1/165.short
4100  - http://www.ajnr.org/content/31/1/165.full
SO  - Am. J. Neuroradiol.2010 Jan 01; 31
AB  - 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.