Matrix metalloproteinases and their inhibitors in different acute stroke subtypes

Vukasović, Ines; Tešija-Kuna, Andrea; Topić, Elizabeta; Supanc, Višnja; Demarin, Vida; Petrovcic, Marija

doi:10.1515/cclm.2006.079

Cited by 28 publications

(28 citation statements)

References 29 publications

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“…The observed low levels of MMP-2 in our study are consistent with other data finding reduced MMP-2 concentrations during the acute phase of stroke compared to controls [48, 49]. In contrast, Chang et al [50 ]demonstrated the coordinate expression of the direct and indirect MMP-2 activators immediately after experimental middle cerebral artery occlusion.…”

Section: Discussionsupporting

confidence: 92%

Single-Nucleotide Polymorphisms of MMP-2 Gene in Stroke Subtypes

et al. 2008

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Background: Matrix metalloproteinases (MMP) are expressed after ischemic stroke. These proteases are responsible for a higher incidence of hemorrhages, are correlated to size of infarction and influence the effects of recombinant tissue plasminogen activator treatment. We therefore evaluated single nucleotide polymorphisms (SNP) of MMP-2 in different subtypes of stroke patients in an association study using a case-control design. Methods: 197 stroke patients were divided according to modified TOAST criteria (small vessel disease, large vessel disease, hemorrhagic stroke and asymptomatic carotid artery stenosis) and compared to 143 controls. Clinical data like age, sex, risk factors and diagnostic results including MRI or cranial CT scans and ultrasound evaluations of intra- and extracranial arteries were obtained. Genotypes of MMP-2 (12 SNP) were compared to controls and DNA samples were analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis. Logistic regression analysis was performed for small vessel disease to test for interactions between markers and defined clinical risk factors. Additionally, MMP-2 serum levels obtained in the first 24 h after stroke were measured. Results: From the MMP-2 gene, 5 markers (rs1030868, rs2241145, rs2287074, rs2287076, rs7201) showed a significant association with small vessel infarcts (p < 0.05) and rs7201:g.C was identified as an independent risk factor by multivariable logistic regression analysis. MMP-2 protein levels were significantly lower in this group (174 ± 48 ng/dl) versus controls (214 ± 56 ng/dl). For other stroke subtypes, no significant association with MMP-2 SNP could be found. Conclusion: Our study demonstrates an association of the MMP-2 gene with the development of lacunar stroke, and no association of MMP-2 with other stroke subtypes.

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Section: Discussionsupporting

confidence: 92%

Single-Nucleotide Polymorphisms of MMP-2 Gene in Stroke Subtypes

et al. 2008

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“…Three months later the TIMP-2 serum levels went back to normal. In contrast to the results of Horstmann and Alvarez-Sabin, Vukasovic et al [23] noted an increase in TIMP-2 levels following stroke (Croatia, n = 250). Rosenberg et al [24] created an experimental stroke model with rats and measured increasing TIMP-2 levels over 14 days with maximum levels on day 5.…”

Section: Discussionmentioning

confidence: 56%

TIMP-2 Gene Polymorphism Is Associated with Intracerebral Hemorrhage

Reuter¹,

Bugert²,

Stroick³

et al. 2009

Cerebrovasc Dis

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Background: Both ischemic stroke and intracerebral hemorrhage are associated with altered expression and activation of matrix metalloproteinases (MMPs). Particularly relevant are MMP-2 and MMP-9. This proteolytic effect is dampened by tissue inhibitors of metalloproteinases (TIMPs). TIMP-2 is an important endogenous inhibitor of MMP-2. Alterations in the TIMP-2 gene expression may contribute to the incidence of ischemic stroke and intracerebral hemorrhage. Methods: TIMP-2 gene SNP –261G/A was genotyped from sequentially recruited stroke patients (n = 356, f/m 151/205, mean age 68.2 years, range 19–100 years) and gender and age matched controls (n = 253, f/m 114/139, mean age 68.5 years, range 32–92 years). The SNP –261G/A was detected after gene sequencing of 95 patients and controls. Furthermore, in a subgroup of 93 patients the serum levels of TIMP-2 were measured during the first 7 days after stroke onset and compared to the genotype. Results: SNP –261G/A in the TIMP-2 gene shows an allele frequency of approximately 39.14%. Homozygosity for allele A is associated significantly with the development of ICH (p = 0.025, OR = 2.020, CI = 1.115–3.661) as compared to heterozygosity and homozygosity for allele G (recessive genotypic model). Concordantly, the serum levels of TIMP-2 showed a nonsignificant decreases, depending on the genotype (p = 0.111). Conclusion: We investigated a SNP 261 base pairs upstream of the start codon in exon 1 of TIMP-2. Our data suggest that carriers of homozygosity for allele A are at increased risk of developing intracerebral hemorrhage.

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“…Acute MMP-9 concentrations have also been related to infarct size, poor neurological outcome, and hemorrhagic transformation complications (63,65,66 ). MMP-9 concentrations assessed at hospital admission have been identified as a predictor of infarct volume as measured with diffusion-weighted MRI (67 ), and the biomarker is further correlated with stroke lesion growth, even with the effective application of thrombolytic therapy (68 ).…”

Section: Matrix Metalloproteinmentioning

confidence: 99%

Stroke Biomarkers: Progress and Challenges for Diagnosis, Prognosis, Differentiation, and Treatment

2010

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Background: Stroke is a devastating condition encompassing a wide range of pathophysiological entities that include thrombosis, hemorrhage, and embolism. Current diagnosis of stroke relies on physician clinical examination and is further supplemented with various neuroimaging techniques. A single set or multiple sets of blood biomarkers that could be used in an acute setting to diagnosis stroke, differentiate between stroke types, or even predict an initial/reoccurring stroke would be extremely valuable. Content: We discuss the current classification, diagnosis, and treatment of stroke, focusing on use of novel biomarkers (either solitary markers or multiple markers within a panel) that have been studied in a variety of clinical settings. Summary: The current diagnosis of stroke remains hampered and delayed due to lack of a suitable mechanism for rapid (ideally point-of-care), accurate, and analytically sensitive biomarker-based testing. There is a clear need for further development and translational research in this area. Potential biomarkers identified need to be transitioned quickly into clinical validation testing for further evaluation in an acute stroke setting; to do so would impact and improve patient outcomes and quality of life.

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Matrix metalloproteinases and their inhibitors in different acute stroke subtypes

Cited by 28 publications

References 29 publications

Single-Nucleotide Polymorphisms of MMP-2 Gene in Stroke Subtypes

Single-Nucleotide Polymorphisms of MMP-2 Gene in Stroke Subtypes

TIMP-2 Gene Polymorphism Is Associated with Intracerebral Hemorrhage

Stroke Biomarkers: Progress and Challenges for Diagnosis, Prognosis, Differentiation, and Treatment

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