TY - JOUR
T1 - Tumor necrosis factor-alpha plays an important role in restenosis development
AU - Monraats, Pascalle S.
AU - Pires, Nuno M. M.
AU - Schepers, Abbey
AU - Agema, Willem R. P.
AU - Boesten, Lianne S. M.
AU - de Vries, Margreet R.
AU - Zwinderman, Aeilko H.
AU - de Maat, Moniek P. M.
AU - Doevendans, Pieter A. F. M.
AU - de Winter, Robbert J.
AU - Tio, René A.
AU - Waltenberger, Johannes
AU - 't Hart, Leen M.
AU - Frants, Rune R.
AU - Quax, Paul H. A.
AU - van Vlijmen, Bart J. M.
AU - Havekes, Louis M.
AU - van der Laarse, Arnoud
AU - van der Wall, Ernst E.
AU - Jukema, J. Wouter
PY - 2005
Y1 - 2005
N2 - 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
AB - 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
U2 - https://doi.org/10.1096/fj.05-4634com
DO - https://doi.org/10.1096/fj.05-4634com
M3 - Article
C2 - 16319143
SN - 0892-6638
VL - 19
SP - 1998
EP - 2004
JO - FASEB Journal
JF - FASEB Journal
IS - 14
ER -