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.

Haplotype, Inflammation, TNFα, Transgenic mice
dx.doi.org/10.1096/fj.05-4634com, hdl.handle.net/1765/65673
FASEB Journal
Department of Psychiatry

Monraats, P.S, Pires, N.M.M, Schepers, A, Agema, W.R.P, Boesten, I, de Vries, M.R, … Jukema, J.W. (2005). Tumor necrosis factor-α plays an important role in restenosis development. FASEB Journal, 19(14), 1998–2004. doi:10.1096/fj.05-4634com