Tumor necrosis factor-α plays an important role in restenosis development

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. TNF alpha, 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 TNF alpha gene was performed. The role of TNF alpha in restenosis was also assessed in ApoE*3-Leiden mice, TNF alpha knockout mice, and by local delivery of a TNF alpha biosynthesis inhibitor, thalidomide. The -238G-1031T haplotype of the TNF alpha gene increased clinical and angiographic risk of restenosis (P = 0.02 and P = 0.002, respectively). In a mouse model of reactive stenosis, arterial TNF alpha mRNA was significantly time-dependently up-regulated. Mice lacking TNF alpha 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 TNF alpha plays an important role in restenosis. Therefore, TNF alpha 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 TNF alpha may be an anti-restenotic target strategy.