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(Stroke. 2007;38:2787.)
© 2007 American Heart Association, Inc.

Original Contributions

Molecular Indices of Apoptosis Activation in Elastase-Induced Aneurysms After Embolization With Platinum Coils

Ramanathan Kadirvel, PhD; Yong-Hong Ding, MD; Daying Dai, MD, PhD; Debra A. Lewis, PhD; Harry J. Cloft, MD, PhD David F. Kallmes, MD

From the Department of Radiology, Mayo Clinic, Rochester, Minn.

Correspondence to David F. Kallmes, MD, Department of Radiology, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905. E-mail Kallmes.david{at}mayo.edu

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- 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-–mediated extrinsic and Bcl-2-mediated intrinsic pathways.

Key Words: apoptosis • endovascular treatment • saccular aneurysms