Analysis of coding sequences for tissue inhibitor of metalloproteinases 1 (TIMP1) and 2 (TIMP2) in patients with aneurysms

Wang, Xiaoju; Tromp, Gerard; Cole, C. William; Verloes, Alain; Sakalihasan, Natzi; Yoon, Sungpil; Kuivaniemi, Helena

doi:10.1016/s0945-053x(99)00008-6

Cited by 47 publications

(34 citation statements)

References 13 publications

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“…Furthermore, polymorphisms in the MMP-3 promoter and the gene for TIMP-1, but not the gene for MMP-9, have been reported to be associated with abdominal aortic aneurysm (39,42). A few patients in our KD study population had extremely high pro-MMP-9 enzyme or pro-MMP-9 protein levels.…”

Section: Vol 10 2003 Elevated Pro-mmp-9 and Timp-1 In Kd 311mentioning

confidence: 77%

Elevated Levels of Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 during the Acute Phase of Kawasaki Disease

Chua

Melish

et al. 2003

Clin Vaccine Immunol

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Kawasaki disease (KD) is an acute, self-limiting, multisystem vasculitis of unknown etiology affecting infants and young children. Unless treated promptly with high-dose intravenous gamma globulin and aspirin, patients frequently develop coronary aneurysms. Previously, matrix metalloproteinase 9 (MMP-9), which is secreted complexed to tissue inhibitor of metalloproteinase 1 (TIMP-1), has been implicated in abdominal aortic aneurysm formation. Since the clinical and pathological features of KD include inflammation and weakening of blood vessels, we analyzed acute-and convalescent-phase paired plasma or serum samples from 31 KD patients, 7 patients who did not completely meet the criteria for KD, and 26 non-KD controls (9 febrile and 17 afebrile patients) for pro-MMP-9 (92 kDa) enzyme activity by gelatin zymography and for active MMP-9 (83 kDa), pro-MMP-9, and TIMP-1 protein levels by enzyme-linked immunosorbent assay. Statistical analysis was performed by using Student t tests, linear regression, and the Wilcoxon rank-sum test. Markedly elevated pro-MMP-9 enzymatic activity, pro-MMP-9 protein levels, and TIMP-1 protein levels were found during the acute phase of illness in patients with clinically established KD and in patients who were suspected of having KD but did not meet all of the criteria. There was no significant difference in active MMP-9 levels. Furthermore, pro-MMP-9 and TIMP-1 protein levels were significantly elevated among KD patients, compared to those of febrile and afebrile non-KD controls. The significantly elevated pro-MMP-9 enzyme and protein levels during the acute phase of KD may reflect vascular remodeling or an inflammatory response to a microbial agent, suggesting a pathophysiological role for MMP-9 in coronary aneurysm formation.

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Section: Vol 10 2003 Elevated Pro-mmp-9 and Timp-1 In Kd 311mentioning

confidence: 77%

Elevated Levels of Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 during the Acute Phase of Kawasaki Disease

Chua

Melish

et al. 2003

Clin Vaccine Immunol

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“…Wang et al 38 have analyzed the sequences of the TIMP-1 and TIMP-2 genes in a mixed North American and European white population with abdominal aortic aneurysm, but also in 1 individual with both aortic and intracranial aneurysms and 4 individuals with intracranial aneurysms. They identified 2 polymorphisms each in TIMP-1 and TIMP-2 and presented preliminary results of different allele frequencies of a nucleotide 573 polymorphism in the TIMP-2 gene between male controls and patients with abdominal aortic aneurysms.…”

Section: Krex Et Al Timp Polymorphisms In Aneurysm Patientsmentioning

confidence: 99%

Tissue Inhibitor of Metalloproteinases-1, −2, and −3 Polymorphisms in a White Population With Intracranial Aneurysms

Krex

Röhl

König

et al. 2003

Stroke

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Background and Purpose-Remodeling of the extracellular matrix seems to be a crucial event in the pathogenesis of cerebral aneurysms. Matrix metalloproteinases are the most important degrading enzymes in the extracellular matrix. Their activity is controlled predominantly by tissue inhibitors of metalloproteinases (TIMPs). To investigate the possible impact of genetic variants within the genes encoding TIMP-1, -2, and -3, we conducted this case-control study. Methods-A study sample was analyzed that comprised 44 patients with intracranial aneurysms and 44, 41, and 40 controls for the analysis of TIMP-1, -2, and -3, respectively. Differences in genotype and allele frequencies of identified polymorphisms were determined. The entire coding regions and parts of the promoter sequences of the TIMP-1, -2, and -3 genes were with using the automated laser fluorescence technique. Results-Nine polymorphisms were identified, 3 located in TIMP-1 (Ϫ19CϾT, 261CϾT, 372TϾC), 4 in TIMP-2 (Ϫ621CϾT, Ϫ596AϾC, Ϫ261GϾA, 303GϾA), and 2 in TIMP-3 (249TϾC, 261CϾT), whereas Ϫ621CϾT, Ϫ596AϾC, and Ϫ261GϾA of the TIMP-2 gene are newly identified polymorphisms. We detected no deviation from Hardy-Weinberg equilibrium in any of the groups. The C allele of the 372TϾC polymorphism was more frequently found in female than in male controls (exact nominal Pϭ0.0012). However, this finding could not be validated by analysis of a second sample of 113 controls (exact nominal Pϭ1.0000). There were no differences in genotype and allele frequencies between any of the other groups. Conclusions-Our analysis of the entire coding region of 3 TIMPs, which are the main inhibitors of metalloproteinase activity in the extracellular matrix, failed to show an association between genetic polymorphisms and an intracranial aneurysm. These data do not support the hypothesis that genetic variants within these genes have an impact on aneurysm development in the white population.

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“…A relative decrease in TIMP expression has been found in aneurysmal aortas. Although this study concluded that this deficiency was not a result of a primary gene mutation (Tilson et al, 1993), more recent studies have identified both a TIMP-1 and TIMP-2 polymorphism to be expressed in higher frequencies in patients with AAA (Ogata et al, 2005;Wang et al 1999). Despite this, the observed single base pair change does not change translation and is therefore unlikely to be involved in the pathogenesis of AAA.…”

Section: Tissue Inhibitors Of Mmp's and Plasminogen Activator Inhibitorsmentioning

confidence: 66%

Pathophysiology of Abdominal Aortic Aneurysm – Genetic Factors and Homocysteine Metabolism

Delaney¹,

Saleem²,

Wong³

et al. 2011

Diagnosis, Screening and Treatment of Abdominal, Thoracoabdominal and Thoracic Aortic Aneurysms

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Analysis of coding sequences for tissue inhibitor of metalloproteinases 1 (TIMP1) and 2 (TIMP2) in patients with aneurysms

Cited by 47 publications

References 13 publications

Elevated Levels of Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 during the Acute Phase of Kawasaki Disease

Elevated Levels of Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 during the Acute Phase of Kawasaki Disease

Tissue Inhibitor of Metalloproteinases-1, −2, and −3 Polymorphisms in a White Population With Intracranial Aneurysms

Pathophysiology of Abdominal Aortic Aneurysm – Genetic Factors and Homocysteine Metabolism

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