Metalloproteinase-2 and -9 in giant cell arteritis: involvement in vascular remodeling.
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.


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.
Department of Medicine, Hospital Universitari Vall d'Hebron, Barcelona, Spain. arodri12@jhmi.edu
Alicia
A
Rodríguez-Pla
Josep A
JA
Bosch-Gil
José
J
Rosselló-Urgell
Pere
P
Huguet-Redecilla
John H
JH
Stone
Miquel
M
Vilardell-Tarres
D000368:Aged; D000369:Aged, 80 and over; D001808:Blood Vessels / Q000201:enzymology / Q000473:pathology; D016022:Case-Control Studies; D004547:Elastic Tissue / Q000201:enzymology / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D013700:Giant Cell Arteritis / Q000201:enzymology* / Q000209:etiology / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia / Q000209:etiology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000502:physiology*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology; D013699:Temporal Arteries / Q000201:enzymology / Q000473:pathology; D014651:Vasa Vasorum / Q000201:enzymology / Q000473:pathology
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9