Tumor necrosis factor-α plays an important role in restenosis development
| Autor: | Monraats, P.S., Pires, N.M.M., Schepers, A., Agema, W.R.P., Boesten, L.S.M., Vries, M.R. de, Zwinderman, A.H., Maat, M.P.M. de, Doevendans, P.A.F.M., Winter, R.J. de, Tio, R.A., Waltenberger, J., Hart, L.M. 't, Frants, R.R., Quax, P.H.A., Vlijmen, B.J.M. van, Havekes, L.M., Laarse, A. van der, Wall, E.E. van der, Jukema, J.W. |
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| Přispěvatelé: | TNO Kwaliteit van Leven |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Male
Biomedical Research Heredity Apolipoprotein E3 Coronary Disease Constriction Pathologic Clinical practice Coronary Angiography Linkage Disequilibrium Percutaneous coronary intervention Mice Ischemia Risk Factors Haplotype TNFα Odds Ratio Biology Health Transgenic mice Angioplasty Transluminal Percutaneous Coronary Risk assessment Mice Knockout Reverse Transcriptase Polymerase Chain Reaction Messenger RNA Angiography Middle Aged Thalidomide Up-Regulation Femoral Artery Gene Expression Regulation Neoplastic Treatment Outcome Screening Regression Analysis Female Adult Genotype Drug delivery system Mice Transgenic Angina Pectoris Coronary Restenosis Knockout mouse Animals Humans Animalia Mus musculus Animal model Genetic Predisposition to Disease Animal experiment RNA Messenger Alleles Aged Inflammation Genetic polymorphism Polymorphism Genetic Restenosis Tumor necrosis factor alpha Tumor Necrosis Factor-alpha Nonhuman Disease Models Animal Haplotypes Multivariate Analysis Disease marker |
| Zdroj: | FASEB Journal, 14, 19, 1998-2004 |
| Popis: | Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. TNFα, a key regulator of inflammatory responses, may exert critical influence on the development of restenosis after PCI. The GENetic DEterminants of Restenosis (GENDER) project included 3104 patients who underwent a successful PCI. Systematic genotyping for six polymorphisms in the TNFα gene was performed. The role of TNFα in restenosis was also assessed in ApoE*3-Leiden mice, TNFα knockout mice, and by local delivery of a TNFα biosynthesis inhibitor, thalidomide. The -238G-1031T haplotype of the TNFα gene increased clinical and angiographic risk of restenosis (P=0.02 and P=0.002, respectively). In a mouse model of reactive stenosis, arterial TNFα mRNA was significantly time-dependently up-regulated. Mice lacking TNFα or treated locally with thalidomide showed a reduction in reactive stenosis (P=0.01 and P=0.005, respectively). Clinical and preclinical data indicate that TNFα plays an important role in restenosis. Therefore, TNFα genotype may be used as a risk marker for restenosis and may contribute to individual patient screening prior to PCI in clinical practice. Inhibition of TNFα may be an anti-restenotic target strategy. ©FASEB. Chemicals / CAS: thalidomide, 50-35-1; RNA, Messenger; Thalidomide, 50-35-1; Tumor Necrosis Factor-alpha |
| Databáze: | OpenAIRE |
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