PMID- 12907822 OWN - NLM STAT- MEDLINE DCOM- 20031006 LR - 20230502 IS - 1524-4628 (Electronic) IS - 0039-2499 (Linking) VI - 34 IP - 9 DP - 2003 Sep TI - Profiles of matrix metalloproteinases, their inhibitors, and laminin in stroke patients: influence of different therapies. PG - 2165-70 AB - BACKGROUND AND PURPOSE: The goal of this study was to determine the temporal profile of several matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), and laminin (an MMP substrate) in human stroke under different treatment paradigms, including thrombolysis and hypothermia. METHODS: We serially measured the serum levels of MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, and laminin in 50 patients with acute ischemic stroke using zymography or enzyme-linked immunosorbent assay. Patients were treated with heparin, therapeutic thrombolysis, or hypothermia. Scandinavian Stroke Scale scores were obtained at baseline. Infarct volume was measured with CT scanning on day 4 after stroke onset. Healthy persons were used as control subjects. RESULTS: MMP-2 and MMP-9 increased during the course of ischemia, whereas intact laminin and TIMP-2 decreased significantly (P<0.05). MMP-9 and laminin levels varied significantly by infarct size (P=0.001) and therapy (P=0.0005). MMP-9 levels were significantly higher in patients treated with tissue plasminogen activator (tPA) compared with patients treated with hypothermia. The cleaved form of MMP-9 was found solely in 4 patients treated with tPA. Intact laminin levels were significantly lower in the tPA group than in the hypothermia group. CONCLUSIONS: Selected MMPs and TIMPs are involved in the pathophysiology of acute stroke. This is also reflected by changes in laminin. Treatment paradigms differentially influence levels of MMP-9 and laminin. Combination therapies explicitly involving MMP inhibition could be of value in future treatment strategies. FAU - Horstmann, Solveig AU - Horstmann S AD - Department of Neurology, Medical School, University of Heidelberg, Germany. FAU - Kalb, Pamela AU - Kalb P FAU - Koziol, James AU - Koziol J FAU - Gardner, Humphrey AU - Gardner H FAU - Wagner, Simone AU - Wagner S LA - eng PT - Clinical Trial PT - Controlled Clinical Trial PT - Journal Article DEP - 20030807 PL - United States TA - Stroke JT - Stroke JID - 0235266 RN - 0 (Laminin) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2) RN - 9005-49-6 (Heparin) RN - EC 3.4.24.- (Collagenases) RN - EC 3.4.24.- (MMP13 protein, human) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM CIN - Stroke. 2003 Sep;34(9):2171-2. PMID: 12933975 MH - Adult MH - Aged MH - Brain Ischemia/blood/diagnostic imaging/therapy MH - Cerebral Infarction/blood/diagnostic imaging/therapy MH - Collagenases/blood MH - Disease Progression MH - Female MH - Heparin/therapeutic use MH - Humans MH - Hypothermia, Induced MH - Laminin/*blood MH - Male MH - Matrix Metalloproteinase 13 MH - Matrix Metalloproteinase 2/blood MH - Matrix Metalloproteinase 3/blood MH - Matrix Metalloproteinase 9/blood MH - Matrix Metalloproteinases/*blood MH - Middle Aged MH - Reference Values MH - Stroke/*blood/diagnostic imaging/therapy MH - Thrombolytic Therapy MH - Tissue Inhibitor of Metalloproteinase-1/*blood MH - Tissue Inhibitor of Metalloproteinase-2/*blood MH - Tomography, X-Ray Computed EDAT- 2003/08/09 05:00 MHDA- 2003/10/08 05:00 CRDT- 2003/08/09 05:00 PHST- 2003/08/09 05:00 [pubmed] PHST- 2003/10/08 05:00 [medline] PHST- 2003/08/09 05:00 [entrez] AID - 01.STR.0000088062.86084.F2 [pii] AID - 10.1161/01.STR.0000088062.86084.F2 [doi] PST - ppublish SO - Stroke. 2003 Sep;34(9):2165-70. doi: 10.1161/01.STR.0000088062.86084.F2. Epub 2003 Aug 7.