Published Online
on July 5, 2005

A more recent version of this article appeared on July 12, 2005

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Submitted on November 6, 2004
Revised on February 13, 2005
Accepted on March 29, 2005

Metalloproteinase-2 and -9 in Giant Cell Arteritis. Involvement in Vascular Remodeling

Alicia Rodríguez-Pla MD, PhD^*, Josep A. Bosch-Gil MD, PhD, José Rosselló-Urgell MD, PhD, Pere Huguet-Redecilla MD, PhD, John H. Stone MD, MPH, and Miquel Vilardell-Tarres MD, PhD

From the Departments of Medicine (A.R.-P., J.A.B.-G., M.V.-T.), Preventive Medicine and Epidemiology (J.R.-U.), and Pathology (P.H.-R.), Hospital Universitari Vall d’Hebron, Barcelona, Spain, and Johns Hopkins Vasculitis Center, Johns Hopkins University School of Medicine, Baltimore, Md (J.H.S.).

^* To whom correspondence should be addressed. E-mail: arodri12{at}jhmi.edu.

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 (n=50) and controls (n=97). MMP-9 was found more frequently in positive than in negative temporal artery biopsies (adjusted odds ratio [OR], 3.20; P=0.01). In contrast, the frequency of MMP-2 was not significantly different between positive and negative biopsies (adjusted OR, 2.18; P=0.22). 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. The expression of MMP by smooth muscle cells implicates these cells as potential secretory cells in GCA.

Key words: temporal arteritis • immunohistochemistry • metalloproteinases • muscle, smooth • vasculitis

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