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Human recombinant tissue‐factor pathway inhibitor prevents the proliferation of cultured human neonatal aortic smooth muscle cells
Author(s) -
Kamikubo Yu-ichi,
Nakahara Yo,
Takemoto Sumiyo,
Hamuro Tsutomu,
Miyamoto Seiji,
Funatsu Akinobu
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00312-8
Subject(s) - tissue factor pathway inhibitor , restenosis , recombinant dna , tissue factor , microbiology and biotechnology , pharmacology , immunology , coagulation , medicine , chemistry , biology , biochemistry , stent , gene
Tissue‐factor pathway inhibitor (TFPI) inhibits the procoagulant activity of the tissue‐factor/factor VIIa complex. It was recently reported that TFPI prevented restenosis following tissue injury in a rabbit atherosclerotic model. In order to clarify the mechanism behind this successful prevention of restenosis, we investigated the direct effect of human recombinant TFPI (h‐rTFPI) on the proliferation of cultured human neonatal aortic smooth muscle cells (hSMC). We found that h‐rTFPI exhibits inhibitory activity toward hSMC proliferation, while h‐rTFPI‐C which lacks the carboxyl (C)‐terminal region does not. Furthermore, we found that h‐rTFPI binds to hSMCs with K d =526 nM but that this binding is inhibited by the addition of the synthetic C‐terminal peptide, Lys 254 –Met 276 , to h‐rTFPI. Thus, the interaction of h‐rTFPI with hSMCs mediated via the C‐terminal region is responsible for the anti‐proliferative action of h‐rTFPI. On the basis of these results, we presume that the anti‐proliferative effect of h‐rTFPI in addition to its anticoagulant function plays a significant role in preventing restenosis following tissue injury.