Matrix metalloproteinases and their inhibitors in different acute stroke subtypes
-
Ines Vukasovic
Abstract
The aim of the study was to determine serum levels of selected matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs) in the acute phase of different stroke types subdivided according to the Oxfordshire Community Stroke Project (OCSP) classification and the possibility of discriminating stroke types according to their levels. The study included 126 patients with acute stroke within the first 24h of symptom onset, and 124 healthy volunteers. The stroke group had lower MMP-2 concentrations and MMP-2/TIMP-2 ratios (p<0.001) but higher TIMP-2 (p<0.001) than controls. The level of MMP-9 and the MMP-9/TIMP-1 ratio were higher in patients with total anterior circulation infarct (TACI) than in patients with other stroke subtypes according to OCSP classification (p=0.0019, p=0.0065, respectively) or in controls (p<0.0001, p=0.0024, respectively). A negative correlation of MMP-2 levels with MMP-9 and MMP-9/TIMP-1 ratio was recorded in all stroke subtypes except for TACI. Receiver operating characteristic analysis showed similar discriminating power for MMP-9 levels and Barthel index in the differential diagnosis of TACI. High MMP-9/TIMP-1 ratio (odds ratio 3.263) was associated with TACI. Our results demonstrate that the MMP-9/TIMP-1 ratio may provide information to help in assessing stroke patients in the future as a baseline biomarker of infarct extent.
References
1. Fassbender K, Mossner R, Motsch L, Kischka U, Grau A, Hennerici M. Circulating selectin- and immunoglobulin-type adhesion molecules in acute ischemic stroke. Stroke 1995; 26:1361–4.10.1161/01.STR.26.8.1361Search in Google Scholar
2. Aoki T, Sumii T, Mori T, Wang X, Lo EH. Blood-brain barrier disruption and matrix metalloproteinase-9 expression during reperfusion injury: mechanical versus embolic focal ischemia in spontaneously hypertensive rats. Stroke 2002; 33:2711–7.10.1161/01.STR.0000033932.34467.97Search in Google Scholar
3. Wagner S, Nagel S, Kluge B, Schwab S, Heiland S, Koziol J, et al. Topographically graded postischemic presence of metalloproteinases is inhibited by hypothermia. Brain Res 2003; 984:63–75.10.1016/S0006-8993(03)03088-9Search in Google Scholar
4. Alvarez B, Ruiz C, Chacon P, Alvarez-Sabin J, Matas M. Serum values of metalloproteinase-2 and metalloproteinase-9 as related to unstable plaque and inflammatory cells in patients with greater than 70% carotid artery stenosis. J Vasc Surg 2004; 40:469–75.10.1016/j.jvs.2004.06.023Search in Google Scholar
5. Beaudeux J-L, Giral F, Bruckert E, Foglietti M-J, Chapman J. Matrix metalloproteinases, inflammation and atherosclerosis: therapeutic perspectives. Clin Chem Lab Med 2004; 42:121–31.Search in Google Scholar
6. Loftus IM, Naylor AR, Goodall S, Crowther M, Jones L, Bell PR, et al. Increased matrix metalloproteinase-9 activity in unstable carotid plaques: a potential role in acute plaque disruption. Stroke 2000; 31:40–7.10.1161/01.STR.31.1.40Search in Google Scholar
7. Rosenberg GA, Estrada EY, Dencoff JE. MMPs and TIMPs are associated with BBB opening after reperfusion in rat brain. Stroke 1998; 29:2189–95.10.1161/01.STR.29.10.2189Search in Google Scholar
8. Sumii T, Lo EH. Involvement of matrix metalloproteinase in thrombolysis-associated hemorrhagic transformation after embolic focal ischemia in rats. Stroke 2002; 33:831–6.10.1161/hs0302.104542Search in Google Scholar
9. Montaner J, Alvarez-Sabin J, Molina C, Angles A, Abilleira S, Arenillas J, et al. Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment. Stroke 2001; 32:1759–66.10.1161/01.STR.32.8.1759Search in Google Scholar
10. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 1991; 337:1521–6.10.1016/0140-6736(91)93206-OSearch in Google Scholar
11. NSA Stroke Prevention Guidelines. A review of guidelines and a multidisciplinary consensus statement from the National Stroke Association. J Am Med Assoc 1999;281:24–31.Search in Google Scholar
12. Mead GE, Lewis SC, Wardlaw JM, Dennis MS, Warlow CP. How well does the Oxfordshire community stroke project classification predict the site and size of the infarct on brain imaging? J Neurol Neurosurg Psychiatry 2000; 68:558–62.10.1136/jnnp.68.5.558Search in Google Scholar PubMed PubMed Central
13. Birkedal-Hansen H. Proteolytic remodeling of extracellular matrix. Curr Opin Cell Biol 1995; 7:728–35.10.1016/0955-0674(95)80116-2Search in Google Scholar
14. Romanic AM, White RF, Arleth AJ, Ohlstein EH, Barone FC. MMP expression increases after cerebral focal ischemia in rats: inhibition of MMP-9 reduces infarct size. Stroke 1998; 29:1020–30.10.1161/01.STR.29.5.1020Search in Google Scholar
15. Asahi M, Wang X, Mori T, Sumii T, Jung JC, Moskowitz MA, et al. Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia. J Neurosci 2001; 21:7724–32.10.1523/JNEUROSCI.21-19-07724.2001Search in Google Scholar
16. Asahi M, Sumii T, Fini ME, Itohara S, Lo EH. Matrix metalloproteinase 2 gene knockout has no effect on acute brain injury after focal ischemia. Neuroreport 2001; 12:3003–7.10.1097/00001756-200109170-00050Search in Google Scholar
17. Horstmann S, Kalb P, Koziol J, Gardner H, Wagner S. Profiles of matrix metalloproteinases, their inhibitors, and laminin in stroke patients: influence of different therapies. Stroke 2003; 34:2165–70.10.1161/01.STR.0000088062.86084.F2Search in Google Scholar
18. Lorenzl S, De Pasquale G, Segal AZ, Beal MF. Dysregulation of the levels of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in the early phase of cerebral ischemia. Stroke 2003; 34:e37–8.10.1161/01.STR.0000075563.45920.24Search in Google Scholar
19. Castellanos M, Leira R, Serena J, Pumar JM, Lizasoain I, Castillo J, et al. Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke 2003; 34:40–6.10.1161/01.STR.0000046764.57344.31Search in Google Scholar
20. Clark AW, Krekoski CA, Bou SS, Chapman KR, Edwards DR. Increased gelatinase A (MMP-2) and gelatinase B (MMP-9) activities in human brain after focal ischemia. Neurosci Lett 1997; 238:53–6.10.1016/S0304-3940(97)00859-8Search in Google Scholar
21. Kuzuya M, Kanda S, Sasaki T, Tamaya-Mori N, Cheng XW, Itoh T, et al. Deficiency of gelatinase a suppresses smooth muscle cell invasion and development of experimental intimal hyperplasia. Circulation 2003; 108:1375–81.10.1161/01.CIR.0000086463.15540.3CSearch in Google Scholar PubMed
22. Montaner J, Alvarez-Sabín J, Molina CA, Anglés A, Abilleira S, Arenillas J, et al. Matrix metalloproteinase (MMP-9) expression is related to hemorrhagic transformation after cardioembolic stroke. Stroke 2001; 32:2762–7.10.1161/hs1201.99512Search in Google Scholar PubMed
23. Montaner J, Molina CA, Monasterio J, Abilleira S, Arenillas JF, Ribó M, et al. Matrix metalloproteinase-9 pretreatment level predicts intracranial hemorrhagic complications after thrombolysis in human stroke. Circulation 2003; 107:598–603.10.1161/01.CIR.0000046451.38849.90Search in Google Scholar
24. Alvarez-Sabin J, Delgado P, Abilleira S, Molina CA, Arenillas J, Ribó M, et al. Temporal profile of matrix metalloproteinases and their inhibitors after spontaneous intracerebral hemorrhage: relationship to clinical and radiological outcome. Stroke 2004; 35:1316–22.10.1161/01.STR.0000126827.69286.90Search in Google Scholar
25. Van den Steen PE, Dubois B, Nelissen I, Rudd PM, Dwek RA, Opdenakker G. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Crit Rev Biochem Mol Biol 2002; 37:375–536.10.1080/10409230290771546Search in Google Scholar
26. Montaner J, Rovira A, Molina CA, Arenillas JF, Ribó M, Chacon P, et al. Plasmatic level of neuroinflammatory markers predict the extent of diffusion-weighted image lesions in hyperacute stroke. J Cereb Blood Flow Metab 2003; 23:1403–7.10.1097/01.WCB.0000100044.07481.97Search in Google Scholar
27. Rosell A, Alvarez-Sabin J, Arenillas JF, Rovira A, Delgado P, Fernandez-Cadenas I, et al. A matrix metalloproteinase protein array reveals a strong relation between MMP-9 and MMP-13 with diffusion-weighted image lesion increase in human stroke. Stroke 2005; 36:1415–20.10.1161/01.STR.0000170641.01047.ccSearch in Google Scholar
28. Lee SR, Tsuji K, Lee SR, Lo EH. Role of matrix metalloproteinases in delayed neuronal damage after transient global cerebral ischemia. J Neurosci 2004; 24:671–8.10.1523/JNEUROSCI.4243-03.2004Search in Google Scholar
29. Avolio C, Ruggieri M, Giuliani F, Liuzzi GM, Leante R, Riccio P, et al. Serum MMP-2 and MMP-9 are elevated in different multiple sclerosis subtypes. J Neuroimmunol 2003; 136:46–53.10.1016/S0165-5728(03)00006-7Search in Google Scholar
30. McGirt MJ, Lynch JR, Blessing R, Warner DS, Friedman AH, Laskowitz DT. Serum von Willebrand factor, matrix metalloproteinase-9, and vascular endothelial growth factor levels predict the onset of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurgery 2002; 51:1128–34 [discussion 1134–5].10.1097/00006123-200211000-00005Search in Google Scholar
31. Dubois B, Leary SM, Nelissen I, Opdenakker G, Giovannoni G, Thompson AJ. Serum gelatinase B/MMP-9 in primary progressive multiple sclerosis patients treated with interferon-beta-1a. J Neurol 2003; 250:1037–43.10.1007/s00415-003-0110-8Search in Google Scholar
32. Correale J, de los Milagros Bassani Molinas M. Temporal variations of adhesion molecules and matrix metalloproteinases in the course of MS. J Neuroimmunol 2003; 140:198–209.10.1016/S0165-5728(03)00204-2Search in Google Scholar
33. Kuyvenhoven JP, Ringers J, Verspaget HW, Lamers CB, van Hoek B. Serum matrix metalloproteinase MMP-2 and MMP-9 in the late phase of ischemia and reperfusion injury in human orthotopic liver transplantation. Transplant Proc 2003; 35:2967–9.10.1016/j.transproceed.2003.10.049Search in Google Scholar
34. Sfiridaki A, Miyakis S, Tsirakis G, Alegakis A, Passam AM, Kandidaki E, et al. Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease. Clin Chem Lab Med 2005; 43:934–8.10.1515/CCLM.2005.160Search in Google Scholar
35. Jung K, Lein M, Laube C, Lichtinghagen R. Blood specimen collection methods influence the concentration and the diagnostic validity of matrix metalloproteinase 9 in blood. Clin Chim Acta 2001; 314:241–4.10.1016/S0009-8981(01)00679-9Search in Google Scholar
36. Alby C, Ben Abdesselam O, Foglietti MJ, Beaudeux JL. Preanalytical aspects regarding the measurement of metalloproteinase-9 and tissue inhibitor or metalloproteinase-1 in blood. Clin Chim Acta 2002; 325:183–6.10.1016/S0009-8981(02)00247-4Search in Google Scholar
©2006 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Natriuretic peptides and evidence-based quality specifications
- Preanalytical variability: the dark side of the moon in laboratory testing
- Clinical relevance of biological variation: the lesson of brain natriuretic peptide (BNP) and NT-proBNP assay
- Hepatorenal syndrome
- Modified Levey-Jennings charts for calculated laboratory tests
- Increased free malondialdehyde concentrations in smokers normalise with a mixed fruit and vegetable juice concentrate: a pilot study
- The exponentially weighted moving average (EWMA) rule compared with traditionally used quality control rules
- Intermethod calibration of alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) results: application to Fibrotest® and Actitest® scores
- Comparison of TEST 1 with SRS 100 and ICSH reference method for the measurement of the length of sedimentation reaction in blood
- Multicenter evaluation of the interference of hemoglobin, bilirubin and lipids on Synchron LX-20 assays
- Technical evaluation of the Beckman Coulter OV-Monitor (CA 125 antigen) immunoassay
- Erythrocyte membrane Na+,K+-ATPase and Mg2+-ATPase activities in subjects with methylenetetrahydrofolate reductase (MTHFR) 677 C→T genotype and moderate hyperhomocysteinaemia. The role of L-phenylalanine and L-alanine
- Matrix metalloproteinases and their inhibitors in different acute stroke subtypes
- Pyrosequencing protocol requiring a unique biotinylated primer
- Detection of antibodies against 60-, 65- and 70-kDa heat shock proteins in paediatric patients with various disorders using Western blotting and ELISA
- Quantitative determination of erythrocyte folate vitamer distribution by liquid chromatography-tandem mass spectrometry
- Time-level relationship between indicators of oxidative stress and Glasgow Coma Scale scores of severe head injury patients
- Stepwise strategies in analysing haematuria and leukocyturia in screening
- Elevation of serum cerebral injury markers correlates with serum choline decline after coronary artery bypass grafting surgery
- Drug screening in urine by cloned enzyme donor immunoassay (CEDIA) and kinetic interaction of microparticles in solution (KIMS): a comparative study
- Release of anandamide from blood cells
- Rapid decrease in plasma D-lactate as an early potential predictor of diminished 28-day mortality in critically ill septic shock patients
- Evaluation of an immunoassay of whole blood sirolimus in pediatric transplant patients in comparison with high-performance liquid chromatography/tandem mass spectrometry
- Sample processing and its preanalytical impact on the measurement of circulating matrix metalloproteinases
- Physiological matrix metalloproteinase (MMP) concentrations: comparison of serum and plasma specimens
- Importance of the functional sensitivity determination of a serum hyaluronic acid assay for the prediction of liver fibrosis in patients with features of the metabolic syndrome
- The dilemma of invasive and non-invasive investigations for adult and paediatric non-alcoholic fatty liver disease: has the time come for a new biochemical marker?
- Is cystatin C a reliable renal marker in trauma?
- On the independence of intraindividual reference values
- Sixth International Symposium on Molecular Diagnostics, Graz, Austria, May 25-27, 2006
Articles in the same Issue
- Natriuretic peptides and evidence-based quality specifications
- Preanalytical variability: the dark side of the moon in laboratory testing
- Clinical relevance of biological variation: the lesson of brain natriuretic peptide (BNP) and NT-proBNP assay
- Hepatorenal syndrome
- Modified Levey-Jennings charts for calculated laboratory tests
- Increased free malondialdehyde concentrations in smokers normalise with a mixed fruit and vegetable juice concentrate: a pilot study
- The exponentially weighted moving average (EWMA) rule compared with traditionally used quality control rules
- Intermethod calibration of alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) results: application to Fibrotest® and Actitest® scores
- Comparison of TEST 1 with SRS 100 and ICSH reference method for the measurement of the length of sedimentation reaction in blood
- Multicenter evaluation of the interference of hemoglobin, bilirubin and lipids on Synchron LX-20 assays
- Technical evaluation of the Beckman Coulter OV-Monitor (CA 125 antigen) immunoassay
- Erythrocyte membrane Na+,K+-ATPase and Mg2+-ATPase activities in subjects with methylenetetrahydrofolate reductase (MTHFR) 677 C→T genotype and moderate hyperhomocysteinaemia. The role of L-phenylalanine and L-alanine
- Matrix metalloproteinases and their inhibitors in different acute stroke subtypes
- Pyrosequencing protocol requiring a unique biotinylated primer
- Detection of antibodies against 60-, 65- and 70-kDa heat shock proteins in paediatric patients with various disorders using Western blotting and ELISA
- Quantitative determination of erythrocyte folate vitamer distribution by liquid chromatography-tandem mass spectrometry
- Time-level relationship between indicators of oxidative stress and Glasgow Coma Scale scores of severe head injury patients
- Stepwise strategies in analysing haematuria and leukocyturia in screening
- Elevation of serum cerebral injury markers correlates with serum choline decline after coronary artery bypass grafting surgery
- Drug screening in urine by cloned enzyme donor immunoassay (CEDIA) and kinetic interaction of microparticles in solution (KIMS): a comparative study
- Release of anandamide from blood cells
- Rapid decrease in plasma D-lactate as an early potential predictor of diminished 28-day mortality in critically ill septic shock patients
- Evaluation of an immunoassay of whole blood sirolimus in pediatric transplant patients in comparison with high-performance liquid chromatography/tandem mass spectrometry
- Sample processing and its preanalytical impact on the measurement of circulating matrix metalloproteinases
- Physiological matrix metalloproteinase (MMP) concentrations: comparison of serum and plasma specimens
- Importance of the functional sensitivity determination of a serum hyaluronic acid assay for the prediction of liver fibrosis in patients with features of the metabolic syndrome
- The dilemma of invasive and non-invasive investigations for adult and paediatric non-alcoholic fatty liver disease: has the time come for a new biochemical marker?
- Is cystatin C a reliable renal marker in trauma?
- On the independence of intraindividual reference values
- Sixth International Symposium on Molecular Diagnostics, Graz, Austria, May 25-27, 2006