Adipokines and thrombosis

Abstract

1. Obesity is a major risk factor for cardiovascular disease. An increased body mass index (BMI) is associated with venous thromboembolism, myocardial infarction, stroke and stent thrombosis after percutaneous interventions. Studies in mouse models of obesity and induced arterial or venous thrombosis have provided insights into the mechanisms involved. 2. In addition to elevated circulating levels of fibrinogen, factor VII and plasminogen activator inhibitor (PAI)-1, changes in platelet biology and function may underlie the increased (athero) thrombotic risk in obesity. These include elevated platelet counts, an increase in mean platelet volume, an increased platelet aggregatory response to agonists and a reversible resistance to the anti-aggregatory effects of nitric oxide and prostacyclin I(2) . 3. Specific adipokines mediate the prothrombotic state in obesity. Of these, leptin enhances both arterial and venous thrombosis by promoting platelet adhesion, activation and aggregation. Leptin also induces tissue factor expression by human neutrophils and other cells. C-Reactive protein enhances the formation of monocyte-platelet aggregates and also promotes P-selectin expression and platelet adhesion to endothelial cells. Further, the adipose tissue is a significant source of tissue factor and PAI-1. Conversely, the circulating levels of adiponectin, a hormone that exerts vasculoprotective, anti-atherosclerotic and antithrombotic effects, are reduced in obese individuals. 4. A better understanding of the interactions of the adipose tissue with circulating and vascular cells and the dissection of the mechanisms linking adipokines to arterial and venous thrombosis may identify obese individuals at particularly high cardiovascular risk and indicate promising vasculoprotective and therapeutic targets.