Title
Tumor necrosis factor-α plays an important role in restenosis development
Author
Monraats, P.S.
Pires, N.M.M.
Schepers, A.
Agema, W.R.P.
Boesten, L.S.M.
de Vries, M.R.
Zwinderman, A.H.
de Maat, M.P.M.
Doevendans, P.A.F.M.
de Winter, R.J.
Tio, R.A.
Waltenberger, J.
't Hart, L.M.
Frants, R.R.
Quax, P.H.A.
van Vlijmen, B.J.M.
Havekes, L.M.
van der Laarse, A.
van der Wall, E.E.
Jukema, J.W.
TNO Kwaliteit van Leven
Publication year
2005
Abstract
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
Subject
Biology Health
Biomedical Research
Haplotype
TNFα
Transgenic mice
Apolipoprotein E3
Messenger RNA
Thalidomide
Tumor necrosis factor alpha
Adult
Aged
Angiography
Animal experiment
Animal model
Clinical practice
Disease marker
Drug delivery system
Genetic polymorphism
Heredity
Knockout mouse
Nonhuman
Percutaneous coronary intervention
Restenosis
Risk assessment
Screening
Aged
Alleles
Angina Pectoris
Angiography
Angioplasty, Transluminal, Percutaneous Coronary
Animals
Constriction, Pathologic
Coronary Angiography
Coronary Disease
Coronary Restenosis
Disease Models, Animal
Female
Femoral Artery
Gene Expression Regulation, Neoplastic
Genetic Predisposition to Disease
Genotype
Haplotypes
Humans
Inflammation
Ischemia
Linkage Disequilibrium
Male
Mice
Mice, Knockout
Mice, Transgenic
Middle Aged
Multivariate Analysis
Odds Ratio
Polymorphism, Genetic
Regression Analysis
Reverse Transcriptase Polymerase Chain Reaction
Risk Factors
RNA, Messenger
Thalidomide
Treatment Outcome
Tumor Necrosis Factor-alpha
Up-Regulation
Animalia
Mus musculus
To reference this document use:
http://resolver.tudelft.nl/uuid:11506bee-65f4-4c8d-9f02-23c7c8aeb89b
DOI
https://doi.org/10.1096/fj.05-4634com
TNO identifier
238864
ISSN
0892-6638
Source
FASEB Journal, 19 (14), 1998-2004
Document type
article