Matrix Metalloproteinases as Novel Disease Markers in Takayasu Arteritis

Matsuyama, Akifumi; Sakai, Naohiko; Ishigami, Masato; Hiraoka, Hisatoyo; Kashine, Susumu; Hirata, Ayumu; Nakamura, Tadashi; Yamashita, Shizuya; Matsuzawa, Yūji

doi:10.1161/01.cir.0000090689.69973.b1

Cited by 142 publications

(97 citation statements)

References 23 publications

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“…Thus urinary MMP excretion is not a reflection of increased systemic inflammation and MMP expression. Previously, in systemic lupus erythematosus, giant cell arteritis, and Takayasu arteritis, elevated protein levels and activity of MMP-9 were found, whereas MMP-2 was elevated in Takayasu arteritis (4,11,13). In Wegener's granulomatosis, Bjerkeli (1) found increased plasma MMP levels, including MMP-2.…”

Section: Discussionmentioning

confidence: 96%

Urinary matrix metalloproteinases reflect renal damage in anti-neutrophil cytoplasm autoantibody-associated vasculitis

Sanders

Huitema²,

Hanemaaijer³

et al. 2007

American Journal of Physiology-Renal Physiology

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Sanders J-S, Huitema MG, Hanemaaijer R, van Goor H, Kallenberg CG, Stegeman CA. Urinary matrix metalloproteinases reflect renal damage in anti-neutrophil cytoplasm autoantibody-associated vasculitis. Am J Physiol Renal Physiol 293: F1927-F1934, 2007. First published September 26, 2007; doi:10.1152/ajprenal.00310.2007.-Renal expression of MMP-2, -9, and tissue inhibitor of MMP-1 (TIMP-1) correlates with histological disease activity in anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV). We studied whether urinary and plasma levels of MMP-2, -9, and TIMP-1 reflect renal expression of these proteins and renal disease-activity in AAV. Urine and plasma samples of patients with AAV who underwent a renal biopsy were collected (n ϭ 32). Urinary activity of MMP-2 and -9 was measured by activity assays. Urinary and plasma levels of MMP-2, MMP-9, and TIMP-1 proteins were measured by ELISA. Healthy controls provided plasma and urine for comparison (n ϭ 31). In patients, the relationship of urinary and plasma levels with renal expression of MMP-2 and MMP-9 and clinical and histological disease activity was studied. Renal MMP expression was compared between patients and controls (n ϭ 8). Urinary MMP-2 and MMP-9 activity and urinary and plasma TIMP-1 levels were significantly higher in patients than in controls. In glomeruli of patients, both MMP-2 and MMP-9 expression reflected active glomerular inflammation. Urinary activity of MMP-2 and MMP-9 did not correlate with renal MMP expression or plasma levels. Urinary MMP activity correlated negatively with glomerular inflammation, but positively with fibrous crescents. Urinary MMP-2 and TIMP-1 levels showed a positive correlation with tubulointerstitial damage and a negative correlation with creatinine clearance. Urinary MMP-2, MMP-9, and TIMP-1 are elevated in AAV but do not reflect renal MMP expression and glomerular inflammation. However, urinary MMP-2 activity and TIMP-1 levels reflect tubulointerstitial damage and correlate negatively with creatinine clearance at biopsy.ANCA-associated vasculitis; crescentic glomerulonephritis; MMP-2; MMP-9; TIMP-1; immunohistochemistry; urinary levels; plasma levels MANY PATIENTS WITH VASCULITIS associated with anti-neutrophil cytoplasmic autoantibodies (ANCA) develop pauci-immune necrotizing crescentic glomerulonephritis, which is frequently associated with rapidly progressive deterioration of renal function (5). Although the pathogenesis of this glomerulonephritis is not precisely known, leukocyte infiltration, matrix degradation, and necrosis are essential steps in disease development. Following institution of immunosuppressive treatment, some glomeruli with active crescentic lesions resolve with improvement of glomerular function, whereas others become acellular and fibrotic leading to permanent loss of glomerular function (8).The role of matrix metalloproteinases (MMPs) in glomerular disease is increasingly appreciated. MMPs mediate both degradation of extracellular matrix components and cell proliferation and fa...

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Section: Discussionmentioning

confidence: 96%

Urinary matrix metalloproteinases reflect renal damage in anti-neutrophil cytoplasm autoantibody-associated vasculitis

Sanders

Huitema²,

Hanemaaijer³

et al. 2007

American Journal of Physiology-Renal Physiology

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“…Usually, surgery or endovascular repair is recommended at a time of quiescent TA disease to avoid complications. 13,24 Matsuyama et al 25 found that increased levels of inflammatory cytokines within the arterial lesions of TA induce production of matrix metalloproteinase (MMP)-3 and MMP-9 from infiltrated mononuclear cells and/or smooth muscle cells, which results in the destruction of elastic fibers in the arterial media. They observed a positive correlation between both MMP-3 and MMP-9 levels and disease activity score, and the elevated levels of MMP-3 and MMP-9 improved when patients entered remission.…”

Section: Discussionmentioning

confidence: 99%

“…They observed a positive correlation between both MMP-3 and MMP-9 levels and disease activity score, and the elevated levels of MMP-3 and MMP-9 improved when patients entered remission. 25 Numano et al 1 advocated that the inflammation caused by TA would result in atherosclerotic lesions of the aorta and arteries. Hypertension, frequently found in patients with TA, may accelerate the atherosclerotic process in the long run.…”

Section: Discussionmentioning

confidence: 99%

Retrospective Analysis of Surgery Versus Endovascular Intervention in Takayasu Arteritis

Saadoun

Lambert²,

Mirault³

et al. 2012

Circulation

231

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“…Stimuli for synthesis are cytokines, which are inflammatory mediators. Thus some studies suggest that MMP values can also be used as markers of disease activity, for example in rheumatoid arthritis, 37 38 Takayasu arteritis, 39 and giant cell arteritis. 40 We found increased levels of MMP-3, MMP-9, and TIMP-1 in our patients as well.…”

Section: Discussionmentioning

confidence: 99%

Accelerated atherosclerosis in patients with Wegener's granulomatosis

Leeuw

2005

Annals of the Rheumatic Diseases

135

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Background: Several autoimmune disorders are complicated by excess cardiovascular disease. In addition to traditional risk factors, non-traditional risk factors such as endothelial activation and excessive vascular remodelling might be determinants of the progression of atherosclerosis in patients with an autoimmune disease. Objective: To evaluate whether patients with Wegener's granulomatosis (WG) have an increased prevalence of atherosclerosis and to determine predisposing factors. Methods: 29 WG patients (19 men; mean (SD) age, 53 (14) years) with inactive disease and 26 controls (16 men; age 53 (15) years) were studied. Common carotid intima-media thickness (IMT) was measured by ultrasound. In all individuals traditional risk factors for cardiovascular disease were determined. High sensitivity C reactive protein (hsCRP) was measured. Endothelial activation was assessed by measuring thrombomodulin, vascular cell adhesion molecule-1, and von Willebrand factor. As a marker of vascular remodelling matrix metalloproteinases (MMP-3 and MMP-9) and TIMP-1 were measured. Results: IMT was increased in WG patients compared with controls (p,0.05). No differences in traditional risk factors and endothelial activation markers between patients and controls were found. Levels of hsCRP, MMPs, and TIMP-1 were increased in WG patients (p,0.05). Conclusions: Increased IMT found in WG patients cannot be explained by an increased prevalence of traditional risk factors. Although endothelial activation markers in WG patients with inactive disease were not increased, the raised levels of hsCRP, MMPs, and TIMP-1 suggest that enhanced inflammation and excessive vascular remodelling are contributing factors in the development of accelerated atherosclerosis in WG.

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Matrix Metalloproteinases as Novel Disease Markers in Takayasu Arteritis

Cited by 142 publications

References 23 publications

Urinary matrix metalloproteinases reflect renal damage in anti-neutrophil cytoplasm autoantibody-associated vasculitis

Urinary matrix metalloproteinases reflect renal damage in anti-neutrophil cytoplasm autoantibody-associated vasculitis

Retrospective Analysis of Surgery Versus Endovascular Intervention in Takayasu Arteritis

Accelerated atherosclerosis in patients with Wegener's granulomatosis

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