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.

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FASEB Journal
Department of Psychiatry

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