Regulation of the procoagulant response to arterial injury.
The last few years have provided increasing evidence to support a major role for TF in the initiation and propagation of thrombosis after acute arterial injury. Although thrombotic occlusion occurs in a small minority of patients undergoing acute coronary interventions or bypass surgery, mural thrombi are likely to be present in almost all cases. These thrombi may stimulate SMC and promote the development of intimal hyperplasia and luminal narrowing. The use of inhibitors of TF and factor VIIa, therefore, may not only be valuable for inhibiting thrombus formation associated with acute arterial interventions, but may also have benefit in attenuating intimal hyperplasia. Although this paper focuses on the role of TF in establishing a procoagulant state after arterial injury, the fibrinolytic system undoubtedly plays a role in balancing the effects of increased TF production in the arterial wall. This is underscored by the success of activators of fibrinolysis (tissue plasminogen activator, streptokinase, urokinase) in revascularization in the setting of acute myocardial infarction and is reviewed elsewhere. Likewise, local regulation of TFPI in the atherosclerotic plaque and injured vessel wall may be important in attenuating the effects of increased TF synthesis and accumulation. It has been assumed that the primary source of active TF after arterial injury is either SMC or invading macrophages and that active TF is anchored to the surface of these cells. Recent data have suggested that the majority of cell-associated TF is either encrypted on the cell surface or present in an intracellular pool. Arterial injury may, therefore, involve the de-encryption of surface TF or the release of intracellular TF. In addition, active vascular TF may be present in microparticles that are not anchored to the arterial wall and may be washed into the circulation. The procoagulant state may be further accentuated by the accumulation of bloodborne TF at sites of arterial injury and in developing thrombi. This TF is likely to arise from circulating leukocytes, including neutrophils and monocytes. These studies suggest that the cellular processing of TF may be an important target for inhibiting thrombotic complications associated with arterial injury and acute coronary events.
Taubman
M B
MB
Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029, USA. m_taubman@smtplink.mssm.edu
Giesen
P L
PL
Schecter
A D
AD
Nemerson
Y
Y
D000818:Animals; D001158:Arteries / Q000293:injuries / Q000473:pathology / Q000502:physiology*; D001161:Arteriosclerosis / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology; D005342:Fibrinolysis; D006801:Humans; D006965:Hyperplasia; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D012333:RNA, Messenger; D013925:Thromboplastin / Q000096:biosynthesis / Q000502:physiology*; D013927:Thrombosis / Q000209:etiology*
D012333:RNA, Messenger; D013925:Thromboplastin