These authors contributed equally to this work.
proMetalloproteinase-10 is associated with brain damage and clinical outcome in acute ischemic stroke
Article first published online: 14 AUG 2013
© 2013 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 11, Issue 8, pages 1464–1473, August 2013
How to Cite
proMetalloproteinase-10 is associated with brain damage and clinical outcome in acute ischemic stroke. J Thromb Haemost 2013; 11: 1464–73., , , , , , .
Manuscript handled by: C. Gachet
Final decision: F. R. Rosendaal, 30 May 2013
- Issue published online: 14 AUG 2013
- Article first published online: 14 AUG 2013
- Accepted manuscript online: 7 JUN 2013 12:38AM EST
- Manuscript Received: 1 FEB 2013
- UTE project CIMA
- Ministerio Ciencia Innovación. Grant Number: SAF2009-12039
- Departamento Salud-Gobierno de Navarra. Grant Number: 40/2007
- Consellería Economía Industria. Grant Number: 10PXIB918282PR
- Consellería Educación. Grant Number: CN2011/010
- Instituto de Salud Carlos III. Grant Numbers: FIS/PS09/00143, PI11/00909, CP12/03121
- Spanish Research Network on Cardiovascular-RECAVA. Grant Number: RD06/0014/0008
- Cerebrovascular Diseases RETICS-INVICTUS. Grant Number: RD12/0014
- biological markers;
- matrix metalloproteinases;
- tumor necrosis factor-alpha
Matrix metalloproteinases (MMPs) mediate tissue injury during stroke but also neurovascular remodeling and we have shown that MMP-10 is involved in atherothrombosis.
The purpose of this study was to examine the relationship between proMMP-10 and clinical outcome, assessing inflammatory and proteolytic markers, in patients with acute ischemic stroke.
We prospectively studied 76 patients with ischemic stroke treated with tPA within the first 3 h from symptom onset, compared with 202 non-tPA-treated ischemic stroke patients and 83 asymptomatic subjects. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). Hemorrhagic transformation (HT) and severe brain edema were diagnosed by cranial CT. Good functional outcome was defined as a modified Rankin scale score ≤ 2 at 90 days. Serum levels of MMP-9, proMMP-10, TIMP-1, tumor necrosis factor-α (TNFα), interleukin-6 and cellular fibronectin were measured at admission. The effect of TNFα on endothelial proMMP-10 was assessed in vitro.
Serum proMMP-10 concentration in ischemic stroke patients, non-treated or treated with t-PA, which was higher than age-matched healthy subjects (P < 0.0001), was independently associated with higher infarct volume, severe brain edema, neurological deterioration and poor functional outcome at 3 months (all P < 0.05), but not with HT. proMMP-10 levels were also independently and positively associated with circulating levels of TNFα (P < 0.0001), which induced its endothelial expression in vitro, both mRNA and protein. MMP-9, however, was only associated with HT and severe edema (all P < 0.05).
Increased serum proMMP-10 after acute ischemic stroke, associated with TNFα, is a new marker of brain damage and poor outcome.