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

Abstract

BACKGROUND AND PURPOSE: The mechanism of aneurysm healing after coiling remains poorly understood. The purpose of the study was to obtain a better understanding of the cellular and molecular events that are associated with aneurysm healing after endovascular coiling in a swine aneurysm model.

MATERIALS AND METHODS: Twenty sidewall aneurysms were created surgically in common carotid arteries in 10 swine. These aneurysms were embolized immediately after creation by using platinum coils by endovascular means. Two and 12 weeks after implantation, aneurysm samples were collected for histologic and biochemical analysis.

RESULTS: All aneurysms were completely or nearly completely occluded angiographically at the time of embolization and at follow-up. At 2 weeks, aneurysm cavities were filled with inflammatory cells and myofibroblasts. At 12 weeks, aneurysm cavities were filled with richly vascularized fibrous tissue and disorganized collagen bundles. The expression of matrix metalloproteinase (MMP)-2 and -9 was found to be elevated at 2 weeks. Expression remained greater than that in control tissue at 12 weeks but was significantly decreased compared with the earlier time point. Expression of tissue inhibitors of MMPs (TIMPs) was diminished at both time points. Expression of vascular cell adhesion molecule-1 (VCAM-1) and vascular endothelial growth factor (VEGF) was elevated at both 2 weeks and 12 weeks. Endothelial nitric oxide synthase expression was not different from that in controls. Transforming growth factor-beta expression was elevated at 2 weeks only.

CONCLUSION: The coil occlusion in this model that is prone to heal is associated with increased expression of MMP-2, MMP-9, VCAM-1, and VEGF, and decreased expression of TIMPs.