Serum Levels of Tissue Inhibitors of Metalloproteinase 2 in Patients With Systemic Sclerosis With Duration More Than 2 Years: Correlation With Cardiac and Pulmonary Abnormalities

Shahin, Amira; Elsawaf, Amani; Ramadan, Shahira; Shaker, Olfat; Amin, Mona; Taha, Mohamed

doi:https://doi.org/10.1155/MI/2006/38458

Mediators of Inflammation

On this page

Abstract References Copyright Related Articles

Research Communication | Open Access

Volume 2006 | Article ID 038458 | https://doi.org/10.1155/MI/2006/38458

Serum Levels of Tissue Inhibitors of Metalloproteinase 2 in Patients With Systemic Sclerosis With Duration More Than 2 Years: Correlation With Cardiac and Pulmonary Abnormalities

Amira Shahin,¹Amani Elsawaf,¹Shahira Ramadan,²Olfat Shaker,³Mona Amin,⁴and Mohamed Taha⁵

Received21 Jul 2006

Revised15 Oct 2006

Accepted15 Oct 2006

Published14 Dec 2006

Abstract

In this study, we measured the serum concentration of TIMP-2 in patients with systemic sclerosis (SSc) and explored its possible correlation with cardiac and pulmonary lesions. We studied 42 patients with SSc, with duration equal to or more than 2 years. CT chest, ECG, echocardiography, and serum TIMP-2 concentration measurement using ELISA technique were performed in all patients and in 25 normal controls. The mean serum levels of TIMP-2 in patients was higher than in controls (P=.005). The mean CT score of dSSc patients with elevated TIMP-2 levels was significantly higher than dSSc patients with normal levels (P=.013). Four patients out of five with elevated TIMP-2 levels showed diastolic dysfunction (80%), compared to 2 out of 15 lSSc patients with normal levels (13.3%), with P=.014. Our research, though involving a small group of patients, points to the probable role of TIMP-2 in the development of pulmonary lesions in dSSc patients and cardiac lesions in lSSc patients with duration equal to or more than 2 years.

References

C Mauch, B Eckes, N Hunzelmann, T Oono, E Kozlowska, and T Krieg, “Control of fibrosis in systemic scleroderma,” Journal of Investigative Dermatology, vol. 100, no. 1, pp. 92S–96S, 1993.
View at: Publisher Site | Google Scholar
J Varga and S A Jimcncz, “Pathogenesis of scleroderma, cellular aspects,” in Systemic Sclerosis, P J Clements and D E Furst, Eds., pp. 304–321, Williams and Wilkins, Baltimore, Md, 1996.
View at: Google Scholar
L Mattila, K Airola, M Ahonen et al., “Activation of tissue inhibitor of metalloproteinases-3 (TIMP-3) mRNA expression in scleroderma skin fibroblasts,” Journal of Investigative Dermatology, vol. 110, no. 4, pp. 416–421, 1998.
View at: Publisher Site | Google Scholar
T Baker, S Tickle, H Wasan, A Docherty, D Isenberg, and J Waxman, “Serum metalloproteinases and their inhibitors: markers for malignant potential,” British Journal of Cancer, vol. 70, no. 3, pp. 506–512, 1994.
View at: Google Scholar
J Uitto, E A Bauer, and A Z Eisen, “Scleroderma. Increased biosynthesis of triple-helical type I and type III procollagens associated with unaltered expression of collagenase by skin fibroblasts in culture,” Journal of Clinical Investigation, vol. 64, no. 4, pp. 921–930, 1979.
View at: Google Scholar
E C LeRoy, “Increased collagen synthesis by scleroderma skin fibroblasts in vitro. A possible defect in the regulation or activation of the scleroderma fibroblast,” Journal of Clinical Investigation, vol. 54, no. 4, pp. 880–889, 1974.
View at: Google Scholar
S A Young-Min, C Beeton, R Laughton et al., “Serum TIMP-1, TIMP-2, and MMP-1 in patients with systemic sclerosis, primary Raynaud's phenomenon, and in normal controls,” Annals of the Rheumatic Diseases, vol. 60, no. 9, pp. 846–851, 2001.
View at: Google Scholar
K Kikuchi, M Kubo, S Sato, M Fujimoto, and K Tamaki, “Serum tissue inhibitor of metalloproteinases in patients with systemic sclerosis,” Journal of the American Academy of Dermatology, vol. 33, no. 6, pp. 973–978, 1995.
View at: Publisher Site | Google Scholar
N Yazawa, K Kikuchi, H Ihn et al., “Serum levels of tissue inhibitor of metalloproteinases 2 in patients with systemic sclerosis,” Journal of the American Academy of Dermatology, vol. 42, no. 1 pt 1, pp. 70–75, 2000.
View at: Publisher Site | Google Scholar
B Dziankowska-Bartkowiak, E Waszczykowska, M Luczyńska, A Zalewska, and A Sysa-Jędrzejowska, “Serum levels of tissue inhibitor of metalloproteinases 2 in systemic sclerosis: a preliminary study,” Medical Science Monitor, vol. 8, no. 2, pp. CR108–CR112, 2002.
View at: Google Scholar
K T Weber, R Pick, J S Janicki, G Gadodia, and J B Lakier, “Inadequate collagen tethers in dilated cardiopathy,” American Heart Journal, vol. 116, no. 6 pt 1, pp. 1641–1646, 1988.
View at: Publisher Site | Google Scholar
Z Gunja-Smith, A R Morales, R Romanelli, and J F Jr Woessner, “Remodeling of human myocardial collagen in idiopathic dilated cardiomyopathy: role of metalloproteinases and pyridinoline cross-links,” American Journal of Pathology, vol. 148, no. 5, pp. 1639–1648, 1996.
View at: Google Scholar
Z Werb and C M Alexander, “Proteinases and matrix degradation,” in Textbook of Rheumatology, W N Kelly, E D Harris, S Ruddy, and C B Sledge, Eds., pp. 248–268, WB Saunders, New York, NY, 1993.
View at: Google Scholar
W G Stetler-Stevenson, “Dynamics of matrix turnover during pathologic remodeling of the extracellular matrix,” American Journal of Pathology, vol. 148, no. 5, pp. 1345–1350, 1996.
View at: Google Scholar
J F Jr Woessner, “Matrix metalloproteinases and their inhibitors in connective tissue remodeling,” FASEB Journal, vol. 5, no. 8, pp. 2145–2154, 1991.
View at: Google Scholar
S C Tyagi, S Kumar, D J Voelker, H K Reddy, J S Janicki, and J J Curtis, “Differential gene expression of extracellular matrix components in dilated cardiomyopathy,” Journal of Cellular Biochemistry, vol. 63, no. 2, pp. 185–198, 1996.
View at: Publisher Site | Google Scholar
B Dziankowska-Bartkowiak, E Waszczykowska, A Zalewska, and A Sysa-Jędrzejowska, “Correlation of endostatin and tissue inhibitor of metalloproteinases 2 (TIMP2) serum levels with cardiovascular involvement in systemic sclerosis patients,” Mediators of Inflammation, vol. 2005, no. 3, pp. 144–149, 2005.
View at: Publisher Site | Google Scholar
A T Masi, G P Rodnan, and T A Medsger, “Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee,” Arthritis and Rheumatism, vol. 23, no. 5, pp. 581–590, 1980.
View at: Google Scholar
C E LeRoy, C Black, R Fleischmajer et al., “Scleroderma (systemic sclerosis): classification, subsets and pathogenesis,” Journal of Rheumatology, vol. 15, no. 2, pp. 202–205, 1988.
View at: Google Scholar
P Clements, P Lachenbruch, J Siebold et al., “Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis,” Journal of Rheumatology, vol. 22, no. 7, pp. 1281–1285, 1995.
View at: Google Scholar
S Morelli, C Barbieri, A Sgreccia et al., “Relationship between cutaneous and pulmonary involvement in systemic sclerosis,” Journal of Rheumatology, vol. 24, no. 1, pp. 81–85, 1997.
View at: Google Scholar
K Takeda, A Hatamochi, H Ueki, M Nakata, and Y Oishi, “Decreased collagenase expression in cultured systemic sclerosis fibroblasts,” Journal of Investigative Dermatology, vol. 103, no. 3, pp. 359–363, 1994.
View at: Publisher Site | Google Scholar
N Yazawa, K Kikuchi, H Ihn et al., “Serum levels of tissue inhibitor of metalloproteinases 2 in patients with systemic sclerosis,” Journal of the American Academy of Dermatology, vol. 42, no. 1 pt 1, pp. 70–75, 2000.
View at: Publisher Site | Google Scholar
L Mattila, K Airola, M Ahonen et al., “Activation of tissue inhibitor of metalloproteinases-3 (TIMP-3) mRNA expression in scleroderma skin fibroblasts,” Journal of Investigative Dermatology, vol. 110, no. 4, pp. 416–421, 1998.
View at: Publisher Site | Google Scholar
K Kikuchi, T Kadono, M Furue, and K Tamaki, “Tissue inhibitor of metalloproteinase 1 (TIMP-1) may be an autocrine growth factor in scleroderma fibroblasts,” Journal of Investigative Dermatology, vol. 108, no. 3, pp. 281–284, 1997.
View at: Publisher Site | Google Scholar
S L Raza and L A Cornelius, “Matrix metalloproteinases: pro- and anti-angiogenic activities,” Journal of Investigative Dermatology Symposium Proceedings, vol. 5, no. 1, pp. 47–54, 2000.
View at: Publisher Site | Google Scholar
V-M Kähäri and U Saarialho-Kere, “Matrix metalloproteinases in skin,” Experimental Dermatology, vol. 6, no. 5, pp. 199–213, 1997.
View at: Google Scholar
J Greene, M Wang, Y E Liu, L A Raymond, C Rosen, and Y E Shi, “Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4,” Journal of Biological Chemistry, vol. 271, no. 48, pp. 30375–30380, 1996.
View at: Publisher Site | Google Scholar
E Toubi, A Kessel, G Grushko, E Sabo, M Rozenbaum, and I Rosner, “The association of serum matrix metalloproteinases and their tissue inhibitor levels with scleroderma disease severity,” Clinical and Experimental Rheumatology, vol. 20, no. 2, pp. 221–224, 2002.
View at: Google Scholar
C S Zurita-Salinas, E Krötzsch, L Díaz De León, and J Alcocer-Varela, “Collagen turnover is diminished by different clones of skin fibroblasts from early- but not late-stage systemic sclerosis,” Rheumatology International, vol. 24, no. 5, pp. 283–290, 2004.
View at: Publisher Site | Google Scholar
P R Brauer and D H Cai, “Expression of tissue inhibitor of metalloproteinases (TIMPs) during early cardiac development,” Mechanisms of Development, vol. 113, no. 2, pp. 175–179, 2002.
View at: Publisher Site | Google Scholar
D A Siwik and W S Colucci, “Regulation of matrix metalloproteinases by cytokines and reactive oxygen/nitrogen species in the myocardium,” Heart Failure Reviews, vol. 9, no. 1, pp. 43–51, 2004.
View at: Publisher Site | Google Scholar
A A González, A M Segura, K Horiba et al., “Matrix metalloproteinases and their tissue inhibitors in the lesions of cardiac and pulmonary sarcoidosis: an immunohistochemical study,” Human Pathology, vol. 33, no. 12, pp. 1158–1164, 2002.
View at: Publisher Site | Google Scholar
S Fujimoto, T Kagoshima, T Nakajima, and K Dohi, “Doppler echocardiographic assessment of left ventricular diastolic function in patients with progressive systemic sclerosis,” Cardiology, vol. 83, no. 4, pp. 217–227, 1993.
View at: Google Scholar
A P Bogdanov, A G Malov, S V Moiseev, and N G Guseva, “The assessment of left ventricular diastolic function in patients with systemic scleroderma by radionuclide ventriculography,” Terapevticheskii Arkhiv, vol. 67, no. 4, pp. 30–32, 1995.
View at: Google Scholar
G Valentini, D F Vitale, A Giunta et al., “Diastolic abnormalities in systemic sclerosis: evidence for associated defective cardiac functional reserve,” Annals of the Rheumatic Diseases, vol. 55, no. 7, pp. 455–460, 1996.
View at: Google Scholar
G Valentini and S Maione, “Cardiopathy in systemic sclerosis,” Recenti Progressi in Medicina, vol. 87, no. 11, pp. 557–63, 1996.
View at: Google Scholar
W A D'Angelo, J F Fries, A T Masi, and L E Shulman, “Pathologic observations in systemic sclerosis (scleroderma). A study of fifty-eight autopsy cases and fifty-eight matched controls,” American Journal of Medicine, vol. 46, no. 3, pp. 428–440, 1969.
View at: Publisher Site | Google Scholar
J B Kostis, J R Seibold, D Turkevich et al., “Prognostic importance of cardiac arrhythmias in systemic sclerosis,” American Journal of Medicine, vol. 84, no. 6, pp. 1007–1015, 1988.
View at: Publisher Site | Google Scholar
W P Follansbee, “The cardiovascular manifestations of systemic sclerosis (scleroderma),” Current Problems in Cardiology, vol. 11, no. 5, pp. 241–298, 1986.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2006 Amira Shahin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation Order printed copies

Views

314

Downloads

797

Citations