title: Shedding of active tissue factor by aortic smooth muscle cells (SMCs) undergoing apoptosis.
abstract: As apoptosis of neo-intimal SMCs is a feature of advanced atherosclerotic plaques, the procoagulant properties of SMCs of synthetic phenotype undergoing apoptosis were investigated. SMCs isolated from rat aorta obtained 10 days after balloon injury, previously found to up-regulate Tissue Factor (TF) and Tissue Factor Inhibitor (TFPI) and to release large amounts of TFPI (Ghrib et al. Thromb Haemost 2002;87:1043-50), were sensitive to the apoptosis induced by Fas-ligand. During this process, surface TF activity rose by a factor 10 over 6 hours, in parallel with a proportional increase in prothrombinase, while TF protein expressed at the membrane significantly decreased. The microparticles (MPs) produced during SMC death bore intact and functional TF, but the release of TFPI did not change, so that the balance shifted to a procoagulant state during apoptosis. Shed MPs enhanced thrombus formation in flowing whole blood over collagen coated-glass slides. Apoptotic SMCs in atherosclerotic plaques represent a reservoir of highly thrombogenic material, released into the blood stream in case of spontaneous or mechanical plaque disruption.
authors.affiliation: Laboratoire d'Hématologie, Pavillon Caubet, Hôpital Purpan, 31059 Toulouse Cedex, France.
authors.forename: Anne-Cécile
authors.initials: AC
authors.lastname: Brisset
authors.forename: Anne-Dominique
authors.initials: AD
authors.lastname: Terrisse
authors.forename: Dominique
authors.initials: D
authors.lastname: Dupouy
authors.forename: Lise
authors.initials: L
authors.lastname: Tellier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pech
authors.forename: Chantal
authors.initials: C
authors.lastname: Navarro
authors.forename: Pierre
authors.initials: P
authors.lastname: Sié
mesh_terms: D000818:Animals; D001011:Aorta / Q000293:injuries / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000209:etiology / Q000473:pathology
chemical_list: D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D013925:Thromboplastin