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Endovascular Treatment of Aneurysms: Healing Mechanisms in a Swine Model Are Associated with Increased Expression of Matrix Metalloproteinases, Vascular Cell Adhesion Molecule-1, and Vascular Endothelial Growth Factor, and Decreased Expression of Tissue Inhibitors of Matrix Metalloproteinases

R. Kadirvela, D. Daia, Y.H. Dinga, M.A. Danielsona, D.A. Lewisa, H.J. Clofta and D.F. Kallmesa

a From the Neuroradiology Research Laboratory, Department of Radiology, Mayo Clinic College of Medicine, Rochester, Minn


Figure 1
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  		Fig 1. A, Angiogram of experimental aneurysm created on the common carotid artery of swine pre-embolization shows contrast filling of the aneurysm dome.

B, Postembolization angiogram of aneurysm with platinum coils. Aneurysm is tightly packed with platinum coils.

C, Angiogram of 12-week follow-up shows complete occlusion of aneurysm from the parent artery, suggesting the formation of a neointimal layer.


Figure 2
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  		Fig 2. Gross photographs showing a thin to moderately thick membranous tissue at the neck of a 2-week aneurysm (A) and a thick membranous tissue at the neck of a 12-week aneurysm (B).


Figure 3
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  		Fig 3. Histologic evaluation of harvested aneurysms at 2 weeks (A–C) and 12 weeks (D and E).

A, Microphotograph showing attenuated inflammatory tissue within the aneurysm dome (H&E, original magnification x100).

B, Microphotograph showing attenuated spindle cells associated with some inflammatory cells within the aneurysm dome (H&E, original magnification x150).

C, Microphotograph showing that all spindle cells within the aneurysm dome are positive for SMA (immunohistochemistry, antibody for {alpha}-SMA, original magnification x150).

D, Microphotograph showing highly vascularized fibrous tissue within the aneurysm dome (H&E, original magnification x60).

E, Microphotograph showing attenuated inflammatory cells associated with numerous thin-walled vessels within the aneurysm dome (H&E, original magnification x100).


Figure 4
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  		Fig 4. A representative gelatin zymogram of MMP-2 and MMP-9 from pigs at 2 weeks (A) and 12 weeks (B) after embolization. Densitometric analysis of gelatin zymogram of pro-MMP-9 (C), active-MMP-9 (D), pro-MMP-2 (E), and active-MMP-2 (F) at both 2-week and 12-week time points. Labels a–g represent P < .05 compared with FA, JV, PPA, and DPA at 2 weeks (a); FA, JV, PPA, and DPA at 12 weeks (b); PA at 2 weeks (c); PA at 12 weeks (d); the neck at 2 weeks (e); the neck at 12 weeks (f); and the dome at 2 weeks (g).


Figure 5
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  		Fig 5. Densitometric analysis of Western blot of TIMP-1 (A) and TIMP-2 (B) expressions at 2-week and 12-week time points. Labels a and b represent P < .05; labels a–g represent P < .05 compared with FA, PPA, PA and DPA at 2 weeks (a); FA, PPA, PA, and DPA at 12 weeks (b); JV at 2 weeks (c); JV at 12 weeks (d); the neck at 2 weeks (e); the neck at 12 weeks (f); and the dome at 2 weeks (g).


Figure 6
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  		Fig 6. Densitometric analysis of Western blot of VCAM-1 (A), VEGF (B), eNOS (C), and TGF-ß (D) expressions at 2-week and 12-week time points. Labels a and b represent P < .05; labels a–g represent P < .05 compared with FA, PPA, PA, and DPA at 2 weeks (a); FA, PPA, PA, and DPA at 12 weeks (b); JV at 2 weeks (c); JV at 12 weeks (d); the neck at 2 weeks (e); the neck at 12 weeks (f); and the dome at 2 weeks (g).





Copyright © 2008 by the American Society of Neuroradiology. Print ISSN: 0195-6108 Online ISSN: 1936-959X