Cited 54 times since 2005 (2.9 per year) source: EuropePMC FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Volume 19, Issue 14, 1 1 2005, Pages 1998-2004 Tumor necrosis factor-alpha plays an important role in restenosis development. Monraats PS, Pires NM, Schepers A, Agema WR, Boesten LS, de Vries MR, Zwinderman AH, de Maat MP, Doevendans PA, de Winter RJ, Tio RA, Waltenberger J, 't Hart LM, Frants RR, Quax PH, van Vlijmen BJ, Havekes LM, van der Laarse A, van der Wall EE, Jukema JW
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. TNFalpha, 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 TNFalpha gene was performed. The role of TNFalpha in restenosis was also assessed in ApoE*3-Leiden mice, TNFalpha knockout mice, and by local delivery of a TNFalpha biosynthesis inhibitor, thalidomide. The -238G-1031T haplotype of the TNFalpha gene increased clinical and angiographic risk of restenosis (P=0.02 and P=0.002, respectively). In a mouse model of reactive stenosis, arterial TNFalpha mRNA was significantly time-dependently up-regulated. Mice lacking TNFalpha 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 TNFalpha plays an important role in restenosis. Therefore, TNFalpha 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 TNFalpha may be an anti-restenotic target strategy.
