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Circulating tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) in systemic sclerosis patients with elevated pulmonary arterial pressure.

Elias GJ, Ioannis M, Theodora P, Dimitrios PP, Despoina P, Kostantinos V, Charalampos K, Vassilios V, Petros SP - Mediators Inflamm. (2009)

Bottom Line: 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).TIMP-4, but not MMP-9, levels were significantly raised in patients with SSc than controls.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.

View Article: PubMed Central - PubMed

Affiliation: Cardiology Department, Laikon General Hospital, University of Athens Medical School, Athens, Greece.

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.

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(a) MMP-9, (b) TIMP-4, and (c) BNP blood levels in SSc patients with diffuse (dSSc) and limited (lSSc) skininvolvement as well as in those patients with pulmonary fibrosis (PF+) comparedto healthy controls (Mann-Whitney test, NS denotesnonsignificant).
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fig1: (a) MMP-9, (b) TIMP-4, and (c) BNP blood levels in SSc patients with diffuse (dSSc) and limited (lSSc) skininvolvement as well as in those patients with pulmonary fibrosis (PF+) comparedto healthy controls (Mann-Whitney test, NS denotesnonsignificant).

Mentions: MMP-9 levels were not different between the whole SSc patient group andcontrols (530 ± 260 ng/mL versus 446 ± 201 ng/mL, resp.), but patientswith diffuse SSc had higher MMP-9 levels than controls (Figure 1(a)) as well as than patients with limitedSSc (587 ± 266 ng/mL versus 393 ± 182 ng/mL, P = .0003). No significant difference was notedbetween patients with lung fibrosis and those without (548 ± 222 ng/mL versus 517 ± 287 ng/mL).


Circulating tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) in systemic sclerosis patients with elevated pulmonary arterial pressure.

Elias GJ, Ioannis M, Theodora P, Dimitrios PP, Despoina P, Kostantinos V, Charalampos K, Vassilios V, Petros SP - Mediators Inflamm. (2009)

(a) MMP-9, (b) TIMP-4, and (c) BNP blood levels in SSc patients with diffuse (dSSc) and limited (lSSc) skininvolvement as well as in those patients with pulmonary fibrosis (PF+) comparedto healthy controls (Mann-Whitney test, NS denotesnonsignificant).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2630404&req=5

fig1: (a) MMP-9, (b) TIMP-4, and (c) BNP blood levels in SSc patients with diffuse (dSSc) and limited (lSSc) skininvolvement as well as in those patients with pulmonary fibrosis (PF+) comparedto healthy controls (Mann-Whitney test, NS denotesnonsignificant).
Mentions: MMP-9 levels were not different between the whole SSc patient group andcontrols (530 ± 260 ng/mL versus 446 ± 201 ng/mL, resp.), but patientswith diffuse SSc had higher MMP-9 levels than controls (Figure 1(a)) as well as than patients with limitedSSc (587 ± 266 ng/mL versus 393 ± 182 ng/mL, P = .0003). No significant difference was notedbetween patients with lung fibrosis and those without (548 ± 222 ng/mL versus 517 ± 287 ng/mL).

Bottom Line: 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).TIMP-4, but not MMP-9, levels were significantly raised in patients with SSc than controls.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.

View Article: PubMed Central - PubMed

Affiliation: Cardiology Department, Laikon General Hospital, University of Athens Medical School, Athens, Greece.

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.

Show MeSH
Related in: MedlinePlus