Z. Wang1, D. W. Ashley1, L. Kong1, J. Kang1, D. K. Nakayama1, P. S. Dale1 1Mercer University School Of Medicine, The Medical Center Navicent Health, Macon,Department Of Surgery,Macon, GA, USA
Introduction: Insertion of a vena cava filter (VCF) is a therapy for preventing patients from fatal pulmonary embolism. But long-term filter placement may cause significant complications including thrombosis, occlusion and dense adherence of the device to the vessel wall. Retrieval, while effective for reducing risk of long-term complications, is limited by intimal hyperplasia and fibrosis in the caval wall. Matrix metalloproteinases (MMPs), especially active MMP-2 and latent MMP-9, have been found and considered to play a key role in smooth muscle cells (SMCs)-enriched neointima and fibrosis caused by balloon angioplasty. However, it is unknown regarding molecular and cellular mechanisms underlying intimal development after VCF insertion. We sought to investigate if VCF insertion would cause elevation and activation of MMP-2 and -9, and if so, if the proteases would be associated with intimal SMCs.
Methods: Filters were placed in pig infrarenal vena cava (VC) for 30 days and then removed. Tissues of normal VC segments and neointimal tissues adherent to the filter struts were collected. Gelatin zymography was used to examine MMP content and activity. Localization of MMP-2, MMP-9 and SMCs in the intimal tissues was analyzed with immunohistology with antibodies to the proteases and smooth muscle alpha-actin.
Results: MMP-2 was found in normal vena cava tissues. The intimal tissues contained higher amount of latent and active MMP-2 than the normal tissues (p<0.05). Moreover, both latent and active forms of MMP-9 were found in the intimal tissues but not in the normal tissues. The intima was composed predominantly of SMCs. In the intimal tissues, significant immunoreactivities of both MMP-2 and -9 were detected and found to be remarkably associated with SMCs.
Conclusion: The present study demonstrates for the first time that VCF implantation causes elevation and activation of MMP-2 and -9, and the proteases are associated with SMC hyperplasia in neointima. Our data suggest that the MMP activity would significantly contribute to development of intimal hyperplasia and matrix remodeling in filter-inserted vena caval walls. MMP-2 and 9 might be therapeutic targets for inhibiting filter-caused intimal overgrowth and improving filter retrieval.