PMID- 14592830 OWN - NLM STAT- MEDLINE DCOM- 20040420 LR - 20220224 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 103 IP - 5 DP - 2004 Mar 1 TI - Inhibition of restenosis by tissue factor pathway inhibitor: in vivo and in vitro evidence for suppressed monocyte chemoattraction and reduced gelatinolytic activity. PG - 1653-61 AB - Activation of inflammatory and procoagulant mechanisms is thought to contribute significantly to the initiation of restenosis, a common complication after balloon angioplasty of obstructed arteries. During this process, expression of tissue factor (TF) represents one of the major physiologic triggers of coagulation that results in thrombus formation and the generation of additional signals leading to vascular smooth muscle cell (VSMC) proliferation and migration. In this study, we have investigated the mechanisms by which inhibition of coagulation at an early stage through overexpression of tissue factor pathway inhibitor (TFPI), an endogenous inhibitor of TF, might reduce restenosis. In a rabbit femoral artery model, percutaneous delivery of TFPI using a recombinant adenoviral vector resulted in a significant reduction of the intimamedia ratio 21 days after injury. Investigating several markers of inflammation and coagulation, we found reduced neointimal expression of monocyte chemoattractant protein-1 (MCP-1), lesional monocyte infiltration, and expression of vascular TF, matrix metalloproteinase-2 (MMP-2), and MMP-9. Moreover, overexpression of TFPI suppressed the autocrine release of platelet-derived growth factor BB (PDGF-BB), MCP-1, and MMP-2 in response to factors VIIa and Xa from VSMCs in vitro and inhibited monocyte TF activity. These results suggest that TFPI exerts its action in vivo through not only thrombotic, but also nonthrombotic mechanisms. FAU - Kopp, Christoph W AU - Kopp CW AD - 2nd Department of Medicine, Division of Angiology, University of Vienna Medical School, Vienna, Austria. christoph.kopp@univie.ac.at FAU - Holzenbein, Thomas AU - Holzenbein T FAU - Steiner, Sabine AU - Steiner S FAU - Marculescu, Rodrig AU - Marculescu R FAU - Bergmeister, Helga AU - Bergmeister H FAU - Seidinger, Daniela AU - Seidinger D FAU - Mosberger, Isabella AU - Mosberger I FAU - Kaun, Christoph AU - Kaun C FAU - Cejna, Manfred AU - Cejna M FAU - Horvat, Reinhard AU - Horvat R FAU - Wojta, Johann AU - Wojta J FAU - Maurer, Gerald AU - Maurer G FAU - Binder, Bernd R AU - Binder BR FAU - Breuss, Johannes M AU - Breuss JM FAU - Ecker, Rupert C AU - Ecker RC FAU - de Martin, Rainer AU - de Martin R FAU - Minar, Erich AU - Minar E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20031030 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Chemokine CCL2) RN - 0 (DNA, Complementary) RN - 0 (Lipoproteins) RN - 0 (Platelet-Derived Growth Factor) RN - 0 (Proto-Oncogene Proteins c-sis) RN - 0 (lipoprotein-associated coagulation inhibitor) RN - 1B56C968OA (Becaplermin) RN - 9035-58-9 (Thromboplastin) RN - EC 3.4.21.21 (Factor VIIa) RN - EC 3.4.21.6 (Factor Xa) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) SB - IM MH - Adenoviridae/genetics MH - Angioplasty MH - Animals MH - Becaplermin MH - Cell Division MH - Cell Movement MH - Chemokine CCL2/biosynthesis/metabolism MH - Cloning, Molecular MH - Constriction, Pathologic MH - DNA, Complementary/metabolism MH - Factor VIIa/metabolism MH - Factor Xa/metabolism MH - *Graft Occlusion, Vascular MH - Humans MH - Immunohistochemistry MH - In Vitro Techniques MH - Inflammation MH - Lipoproteins/pharmacology MH - Matrix Metalloproteinase 2/biosynthesis/metabolism MH - Microscopy, Confocal MH - Monocytes/*cytology/metabolism MH - Muscle, Smooth, Vascular/cytology MH - Myocytes, Smooth Muscle/cytology MH - Platelet-Derived Growth Factor/biosynthesis/metabolism MH - Precipitin Tests MH - Proto-Oncogene Proteins c-sis MH - Rabbits MH - Reverse Transcriptase Polymerase Chain Reaction MH - Thromboplastin/*antagonists & inhibitors MH - Time Factors MH - Transfection MH - Transgenes MH - U937 Cells EDAT- 2003/11/01 05:00 MHDA- 2004/04/21 05:00 CRDT- 2003/11/01 05:00 PHST- 2003/11/01 05:00 [pubmed] PHST- 2004/04/21 05:00 [medline] PHST- 2003/11/01 05:00 [entrez] AID - S0006-4971(20)50075-X [pii] AID - 10.1182/blood-2003-04-1148 [doi] PST - ppublish SO - Blood. 2004 Mar 1;103(5):1653-61. doi: 10.1182/blood-2003-04-1148. Epub 2003 Oct 30.