Mediators of Inflammation
Volume 2008 (2008), Article ID 164134, 8 pages
doi:10.1155/2008/164134
Clinical Study

Circulating Tissue Inhibitor of Matrix Metalloproteinase-4 (TIMP-4) in Systemic Sclerosis Patients with Elevated Pulmonary Arterial Pressure

Elias J. Gialafos,1,2 Ioannis Moyssakis,1 Theodora Psaltopoulou,3 Dimitrios P. Papadopoulos,1 Despoina Perea,2 Kostantinos Vlasis,2 Charalampos Kostopoulos,4 Vassilios Votteas,1 and Petros P. Sfikakis2

1Cardiology Department, Laikon General Hospital, University of Athens Medical School, 115 27 Athens, Greece
2First Department of Propaedeutic and Internal Medicine, University of Athens Medical School, 115 27 Athens, Greece
3Department of Hygiene and Epidemiology, University of Athens Medical School, 115 27 Athens, Greece
4Pulmonary Unit, Department of Therapeutics, University of Athens Medical School, 115 27 Athens, Greece

Received 31 May 2008; Revised 14 October 2008; Accepted 28 October 2008

Academic Editor: Yona Keisari

Copyright © 2008 Elias J. Gialafos 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.

Abstract

Decreased levels of matrix metalloproteinases (MMPs) or excess levels of their tissue inhibitors (TIMPs) may contribute to dysregulation of extracellular matrix turnover in systemic sclerosis (SSc). In a cross-sectional study of 106 SSc patients, we measured serum levels of TIMP-4 which is preferentially expressed in cardiovascular structures and searched for correlations with simultaneously performed echocardiography measurements of pulmonary artery systolic pressure (PASP), myocardial performance, and pulmonary function tests. TIMP-4, but not MMP-9, levels were significantly raised in patients with SSc than controls. However, in the subgroup of patients with PASP measurements lower to 40 mmHg (n=69), TIMP-4 levels were comparable to controls irrespective of the presence of diffuse or limited skin involvement, or lung fibrosis. Individual PASP measurements suggestive of pulmonary hypertension were associated with increased TIMP-4 serum levels (P=.03), independently of age, extent of skin sclerosis, or lung fibrosis, suggesting a cardiopulmonary vasculature-specific role of TIMP-4 activation in SSc.