Induction of tissue factor in the arterial wall during recurrent thrombus formation.
OBJECTIVE
Tissue factor (TF) is normally expressed at low levels in the media of blood vessels, but it is readily induced after vessel injury. It is not known whether vascular damage per se or thrombus formation is responsible for this phenomenon.


RESULTS
Cyclic flow variations (CFVs), attributable to recurrent thrombus formation, were induced in stenotic rabbit carotid arteries with endothelial injury. CFVs were observed for 30 minutes and 2, 4, and 8 hours in different groups of animals. Another group of rabbits pretreated with hirudin before inducing arterial damage to inhibit thrombus formation was observed for 8 hours. Arterial sections were immunostained for TF. Undamaged arteries served as controls. In additional rabbits, in situ hybridization experiments were performed. No TF expression was observed in the media of control vessels, whereas a progressive increase in TF mRNA and protein expression was observed in carotid arteries as CFVs progressed. No increase in TF expression was observed in animals pretreated with hirudin. In vitro experiments demonstrated that TF mRNA is induced in smooth muscle cells stimulated with activated platelets as well as with some platelet-derived mediators.


CONCLUSIONS
This phenomenon may contribute to sustain intravascular thrombus formation after the initial thrombogenic stimulus.
D'Andrea
Davide
D
Division of Cardiology, University of Naples, Federico II, Italy.
Ravera
Marta
M
Golino
Paolo
P
Rosica
Annamaria
A
De Felice
Mario
M
Ragni
Massimo
M
Cirillo
Plinio
P
Vigorito
Francesco
F
Corcione
Nicola
N
Tommasini
Paola
P
Gargiulo
Annarita
A
Piro
Orlando
O
Calabró
Paolo
P
Chiariello
Massimo
M
D000818:Animals; D001792:Blood Platelets / Q000737:chemistry / Q000502:physiology; D002339:Carotid Arteries / Q000737:chemistry / Q000473:pathology; D002341:Carotid Artery Thrombosis / Q000378:metabolism* / Q000473:pathology; D016893:Carotid Stenosis / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D017403:In Situ Hybridization / Q000379:methods; D009000:Monocytes / Q000737:chemistry / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000737:chemistry / Q000473:pathology; D010972:Platelet Activating Factor / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D012008:Recurrence; D012039:Regional Blood Flow / Q000502:physiology; D013925:Thromboplastin / Q000096:biosynthesis* / Q000378:metabolism; D017539:Tunica Intima / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D017540:Tunica Media / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology
D010972:Platelet Activating Factor; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D013925:Thromboplastin