Role of Risk Factors in the Modulation of Tissue Factor Activity and Blood Thrombogenicity
- 25 February 2003
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 107 (7), 973-977
- https://doi.org/10.1161/01.cir.0000050621.67499.7d
Abstract
Background— Several studies suggest a role for an increased circulating pool of tissue factor (TF) in atherothrombotic diseases. Furthermore, certain cardiovascular risk factors, such as diabetes, hyperlipemia, and smoking, are associated with a higher incidence of thrombotic complications. We hypothesized that the observed increased blood thrombogenicity (BT) observed in patients with type 2 diabetes mellitus may be mediated via an increased circulating tissue factor activity. We have extended our study to smokers and hyperlipidemic subjects. Methods and Results— Poorly controlled patients with type 2 diabetes mellitus (n=36), smokers (n=10), and untreated hyperlipidemic subjects (n=10) were studied. Circulating TF was immunocaptured from plasma, relipidated, and quantified by factor Xa (FXa) generation in the presence of factor VIIa. BT was assessed as thrombus formation on the Badimon perfusion chamber. Patients with improvement in glycemic control showed a reduction in circulating TF (362±135 versus 243±74 pmol/L per min FXa, P =0.0001). A similar effect was observed in BT (15 445±1130 versus 12 072±596 μm/mm 2 , P =0.01). Two hours after smoking 2 cigarettes, TF was increased (217±72 versus 283±106 pmol/L per min FXa, P =0.003). Hyperlipidemic subjects showed higher TF (237±63 versus 195±44 pmol/L per min FXa, P =0.035) than healthy volunteers. Conclusions— These findings suggest that high levels of circulating TF may be the mechanism of action responsible for the increased thrombotic complications associated with the presence of these cardiovascular risk factors. These observations strongly emphasize the usefulness of the management of the patients based on their global risk assessment.This publication has 17 references indexed in Scilit:
- Fluvastatin Reduces Tissue Factor Expression and Macrophage Accumulation in Carotid Lesions of Cholesterol-Fed Rabbits in the Absence of Lipid LoweringArteriosclerosis, Thrombosis, and Vascular Biology, 2002
- Cholesterol-induced Thrombogenicity of the Vessel Wall: Inhibitory Effect of FluvastatinThrombosis and Haemostasis, 2002
- Thrombogenic potential of human coronary atherosclerotic plaquesBlood, 2001
- Blood thrombogenicity in type 2 diabetes mellitus patients is associated with glycemic controlJournal of the American College of Cardiology, 2001
- Statins and cardiovascular diseases: the multiple effects of lipid-lowering therapy by statinsAtherosclerosis, 2000
- Role of platelets in tissue factor expression by monocytes in normal and hypercholesterolemic subjects. In vitro effect of cerivastatinInternational Journal of Clinical and Laboratory Research, 2000
- Vascular-Bed–Specific Hemostasis and Hypercoagulable StatesThe New England Journal of Medicine, 1999
- The Pathogenesis of Coronary Artery Disease and the Acute Coronary SyndromesThe New England Journal of Medicine, 1992
- The Pathogenesis of Coronary Artery Disease and the Acute Coronary SyndromesThe New England Journal of Medicine, 1992
- Influence of arterial damage and wall shear rate on platelet deposition. Ex vivo study in a swine model.Arteriosclerosis: An Official Journal of the American Heart Association, Inc., 1986