Metalloproteinase-2 and -9 in Giant Cell Arteritis

Abstract

Background-Both matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) have been postulated to play roles in the pathophysiology of giant cell arteritis (GCA) because of their ability to degrade elastin. Understanding the specific mediators of arterial damage in GCA could lead to new therapeutic targets in this disease. Methods and Results-Temporal artery biopsy specimens were obtained from 147 consecutive patients suspected of GCA. Clinical and histopathological data were collected according to protocol. Using immunohistochemistry, we compared the expression of MMP-2 and MMP-9 in the temporal artery biopsies of both GCA cases (nϭ50) and controls (nϭ97). MMP-9 was found more frequently in positive than in negative temporal artery biopsies (adjusted odds ratio [OR], 3.20; Pϭ0.01). In contrast, the frequency of MMP-2 was not significantly different between positive and negative biopsies (adjusted OR, 2.18; Pϭ0.22). Both MMP-2 and MMP-9 were found in macrophages and giant cells near the internal elastic lamina and in smooth muscle cells and myofibroblasts of the media and intima. MMP-9 was also found in the vasa vasorum. MMP-9 but not MMP-2 was associated with internal elastic lamina degeneration, intimal hyperplasia, and luminal narrowing, even after adjustment for possible confounding variables. Conclusions-MMP-9 appears more likely than MMP-2 to be involved in the pathophysiology of GCA. MMP-9 not only participates in the degradation of elastic tissue but also is associated with intimal hyperplasia, subsequent luminal narrowing, and neoangiogenesis.

Translational Mini-Review Series on Immunology of Vascular Disease: Mechanisms of vascular inflammation and remodelling in systemic vasculitis

“…Gelatinase activation and proteolytic activity favour leucocyte infiltration and vessel injury. Nevertheless, enzyme action is critical for artery repair [27,28], and macrophages produce trophic and angiogenic factors, such as vascular endothelial growth factor and platelet-derived growth factor which recruit neovessels [7,29] and provide an additional port of entrance, besides the vasa vasorum capillary network of the adventitia for leucocytes.…”

Giant cell arteritis: a systemic vascular disease

“…Macrophages in the media cause damage to the arterial wall through secretion of metalloproteinases and reactive oxygen intermediates. 24,25 These processes lead to fragmentation of the internal elastic lamina, to weakening of the arterial wall, and are probably the basis for development of aneurysms and dissections. When GCA causes arterial stenosis and ischemia, this is due to marked, concentric thickening of the intima.…”

Loss of Elastic Fiber Integrity and Reduction of Vascular Smooth Muscle Contraction Resulting From the Upregulated Activities of Matrix Metalloproteinase-2 and -9 in the Thoracic Aortic Aneurysm in Marfan Syndrome

“…9,10 MMP-2 and -9, known for their roles in degrading elastic fibers, have been suggested to be involved in the pathological vascular remodeling. 10 The balance between MMP-2/-9 and the tissue inhibitor of MMP-1 (TIMP-1)/-2 tightly governs matrix remodeling and is believed to play a central role in the pathogenesis of abdominal aortic aneurysm. [11][12][13][14][15] Activation of TGF-␤ and the concomitant upregulation of various MMPs and TIMPs have been suggested to be associated with the increased apoptosis, impaired progenitor cell recruitment, and abnormal directional migration, which are likely to contribute to aneurysm development in MFS.…”