TY - JOUR
T1 - Intrinsic pathway-mediated apoptosis in elastase-induced aneurysms in rabbits
AU - Kadirvel, R.
AU - Ding, Y. H.
AU - Dai, D.
AU - Lewis, D. A.
AU - Kallmes, David F.
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
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U2 - 10.3174/ajnr.A1781
DO - 10.3174/ajnr.A1781
M3 - Article
C2 - 19749227
AN - SCOPUS:75749130766
SN - 0195-6108
VL - 31
SP - 165
EP - 169
JO - American Journal of Neuroradiology
JF - American Journal of Neuroradiology
IS - 1
ER -