Dataset Information

Tissue Inhibitor of Matrix Metalloproteinase 1 Increases With Ageing and Can Be Associated With Stroke?- Nested Case-Control Study.

ABSTRACT: Background: Increase of collagen in the extracellular matrix occurs with ageing. We investigated whether a collagen marker, tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), was associated with risk of stroke. Methods?and?Results: In a nested case-control study of 953 subjects from the general population, we evaluated determinants of TIMP-1 level and stroke risk. Mean subject age was 65.7±8.6 years (53.0% men); TIMP-1 was 72.4±28.2 pg/mL in the control group and 75.3±30.9 pg/mL in the stroke group. The relationship between TIMP-1 quartile and stroke was J-curved. Subjects in the highest TIMP-1 quartile (?89 ng/mL) had a significantly higher OR of stroke (59-72 ng/mL; OR, 1.90; 95% CI: 1.09-3.31, P=0.023) than those in the second TIMP-1 quartile, and this tended toward significance even after adjusting for confounding factors (P=0.059). Elevation of serum TIMP-1 became more marked after age 65 years. On multiple linear regression analysis, significant determinants of TIMP-1 were older age (B=0.21 per 1 year; 95% CI: 0.52-1.07, P<0.001) and higher systolic blood pressure (SBP; B=0.19 per 1 mmHg, 95% CI: 0.08-0.42, P=0.004). Conclusions: TIMP-1 increased with ageing and with SBP, and can be associated with stroke.

SUBMITTER: Ishikawa J

PROVIDER: S-EPMC7897566 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Tissue Inhibitor of Matrix Metalloproteinase 1 Increases With Ageing and Can Be Associated With Stroke　- Nested Case-Control Study.

Ishikawa Joji J Hirose Hideo H Ishikawa Shizukiyo S

Circulation reports 20191011 11

Background: Increase of collagen in the extracellular matrix occurs with ageing. We investigated whether a collagen marker, tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), was associated with risk of stroke. Methods and Results: In a nested case-control study of 953 subjects from the general population, we evaluated determinants of TIMP-1 level and stroke risk. Mean subject age was 65.7±8.6 years (53.0% men); TIMP-1 was 72.4±28.2 pg/mL in the control group an ...[more]

PMID: 33693092

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Project description:Matrix metalloproteinase-2 (MMP-2) expression is often up-regulated in advanced cancers and known to play an important role in tumor angiogenesis. We previously showed that adenoviral-mediated delivery of siRNA for MMP-2 (Ad-MMP-2-Si) inhibited lung cancer growth, angiogenesis, and metastasis. In this study, we investigated the signaling mechanisms involved in Ad-MMP-2-Si-mediated inhibition of angiogenesis. Ad-MMP-2-Si treatment inhibited neovascularization in vivo as determined by mouse dorsal air sac model, and conditioned medium from Ad-MMP-2-Si-infected A549 lung cancer cells (Ad-MMP-2-Si-CM) inhibited endothelial tube formation in vitro. Ad-MMP-2-Si-CM decreased proliferation as determined by Ki-67 immunofluorescence and induced apoptosis in endothelial cells as determined by terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) assay. Furthermore, Ad-MMP-2-Si-CM inhibited AKT phosphorylation and induced phosphorylation of extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase in endothelial cells. Overexpression of constitutively active AKT reversed the Ad-MMP-2-Si-CM-mediated inhibition of tube formation and induction of ERK phosphorylation. Conversely, Ad-MMP-2-Si-CM induced tissue inhibitor of metalloproteinase (TIMP) 3 expression, and the interaction of vascular endothelial growth factor 2 and TIMP-3 was determined by coimmunoprecipitation experiments. TIMP-3 induction was mediated by ERK activation. In addition, electrophoretic mobility shift and chromatin immunoprecipitation assays show that Sp1 transcription factor mediated Ad-MMP-2-Si-CM-stimulated increase of TIMP-3. Vasculature destruction was confirmed with colocalization studies with TUNEL and an endothelial marker, CD31, in tumor sections of Ad-MMP-2-Si-treated mice. Our data collectively suggest that MMP-2 inhibition induces endothelial apoptosis in vivo and inhibits endothelial tube formation. These experiments provide the first evidence that inhibition of p-AKT and induction of p-ERK1/2 are crucial events in the induction of TIMP-3-mediated endothelial apoptosis in MMP-2 inhibited lung tumors.

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Tissue Inhibitor of Matrix Metalloproteinase 1 Increases With Ageing and Can Be Associated With Stroke?- Nested Case-Control Study.

Publications

Tissue Inhibitor of Matrix Metalloproteinase 1 Increases With Ageing and Can Be Associated With Stroke　- Nested Case-Control Study.

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Dataset Information

Tissue Inhibitor of Matrix Metalloproteinase 1 Increases With Ageing and Can Be Associated With Stroke?- Nested Case-Control Study.

Publications

Tissue Inhibitor of Matrix Metalloproteinase 1 Increases With Ageing and Can Be Associated With Stroke - Nested Case-Control Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Tissue Inhibitor of Matrix Metalloproteinase 1 Increases With Ageing and Can Be Associated With Stroke　- Nested Case-Control Study.