New insights into the role of adipose tissue in thrombosis

Abstract

Central obesity is independently associated with an elevated risk of cardiovascular disease, particularly thrombotic complications. Increasing data supports a link between excess body weight and the risk to suffer acute myocardial infarction, stent thrombosis after percutaneous interventions, ischemic stroke and vein thrombosis. Experimental and in vitro data have provided insights as to the mechanisms currently presumed to increase the thrombotic risk in obese subjects. Obesity is characterized by a chronic low grade inflammation and systemic oxidative stress that eventually damage the endothelium losing its antithrombotic properties. Obesity also stimulates the expression of leptin and attenuates adiponectin release, a protective adipokine. Although the contribution of adipokines to thrombosis has been questioned, recent work has suggested that they enhance platelet activation and, although to a lesser extent, induce the coagulation cascade through tissue factor (TF) expression. Increased body weight also impairs platelet sensitivity to insulin signaling and enhances the production of bioactive isoprostanes further promoting platelet reactivity. Finally, obese subjects have shown elevated circulating levels of von Willebrand factor, TF, factor VII and VIII, and fibrinogen, favoring a mild-to-moderate hypercoagulable state, and, on the other hand, increased secretion of plasminogen activator inhibitor (PAI)-1 and thrombin activatable fibrinolysis inhibitor (TAFI) contributing to impair the fibrinolytic system. In the present review, we provide an overview of the impact of excess body weight on thrombosis. We will focus on the link between dysfunctional adipose tissue and endothelial damage, platelet reactivity, enhanced coagulation and impaired fibrinolysis; mechanisms currently recognized to increase arterial thrombotic risk in obese subjects.

A Combination of Proteomic Approaches Identifies A Panel of Circulating Extracellular Vesicle Proteins Related to the Risk of Suffering Cardiovascular Disease in Obese Patients

“…Adiponectin is an important adipocytokine that plays a crucial role in glucose and lipid metabolism, inflammation, and oxidative stress. Accordingly, high concentrations of adiponectin have been associated with a reduction in the risk of coronary artery disease . Regarding our data, we identified adiponectin as being downregulated in EVs from obese patients pointing toward an increased cardiovascular risk.…”

“…showed increased levels of fibrinogen, tissue factor, and P‐selectin in MVs from diabetes type 2 patients, suggesting their involvement in activation of pathways that contribute to thrombosis, inflammation, and atherosclerosis. Overall, fibrinogen has been described as a potential biomarker for obesity and CVD …”

“…It is noteworthy that adiponectin was previously found to be involved in obesity . Adiponectin is an important adipocytokine that plays a crucial role in glucose and lipid metabolism, inflammation, and oxidative stress.…”

Mendelian Randomization Study of Obesity and Cerebrovascular Disease

“…Low‐grade inflammation and systemic oxidative stress have proven to be damaging for the endothelium, shifting it toward a prothrombotic state. Platelet reactivity, enhanced coagulation, and impaired fibrinolysis are other recognized mechanisms . Our results demonstrating increased risk for SVS and nonlobar ICH on the one hand and for LAS on the other suggest that both cerebral microvascular disruption and accelerated atherosclerosis leading to stroke may be triggered by obesity.…”

Application of Extracellular Vesicles Proteomics to Cardiovascular Disease: Guidelines, Data Analysis, and Future Perspectives

“…[125] It has been described as a potential biomarker for CVD. [126][127][128] Remarkably, the γ chain has a special interest because it contains multiple epitopes that interact with integrins, and plays a critical role in platelet aggregation, inflammation, and wound healing. [67] A2MG plays an important role in thrombogenesis and fibrinolysis.…”