title: Circulating tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) in systemic sclerosis patients with elevated pulmonary arterial pressure.
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.
authors.affiliation: Cardiology Department, Laikon General Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Gialafos J
authors.initials: GJ
authors.lastname: Elias
authors.forename: Moyssakis
authors.initials: M
authors.lastname: Ioannis
authors.forename: Psaltopoulou
authors.initials: P
authors.lastname: Theodora
authors.forename: Papadopoulos P
authors.initials: PP
authors.lastname: Dimitrios
authors.forename: Perea
authors.initials: P
authors.lastname: Despoina
authors.forename: Vlasis
authors.initials: V
authors.lastname: Kostantinos
authors.forename: Kostopoulos
authors.initials: K
authors.lastname: Charalampos
authors.forename: Votteas
authors.initials: V
authors.lastname: Vassilios
authors.forename: Sfikakis P
authors.initials: SP
authors.lastname: Petros
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D011651:Pulmonary Artery / Q000503:physiopathology*; D011658:Pulmonary Fibrosis / Q000097:blood / Q000503:physiopathology; D012595:Scleroderma, Systemic / Q000097:blood* / Q000503:physiopathology; D013599:Systole; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood* / Q000502:physiology; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D020780:Matrix Metalloproteinase 9; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4