THE EFFECT OF OBESITY ON VTE PATHOGENESIS Clause Samples

THE EFFECT OF OBESITY ON VTE PATHOGENESIS. The physical aspects of increased body weight contribute to a higher risk of VTE due to decreased venous return and immobility. Increased BMI and waist-to-hip ratio (WHR) are associated with increased fibrinogen, which promotes fibrin formation, platelet aggregation and plasma viscosity, and increased plasminogen activating factor inhibitor-1 (PAI-1), which decreases fibrin degradation (▇▇▇▇▇▇-▇▇▇▇▇▇▇▇▇, 2011) Both fibrinogen and PAI-1 have been demonstrated to be higher in patients with primary and recurrent VTE, although statistical differences did not exist after controlling for BMI and other confounders. (▇▇▇▇ et al., 2002) Tissue factor (TF) is a 47 kDa transmembrane glycoprotein which initiates the coagulation cascade. It has two isoforms, an insoluble cytokine receptor, which functions as an integrin in intracellular signalling and cell migration, and a soluble isoform, which regulates angiogenesis and monocyte recruitment. Inflammatory mediators are able to induce and upregulate the soluble TF, thus increase their levels in the vasculature. (▇▇▇▇▇ et al., 2001; ▇▇▇▇▇ & ▇▇▇, 2015) Plasma TF levels have been used as a biomarker for the severity of microvascular disease in patients with type two diabetes. Additionally, mice experiments have demonstrated an association between obesity and both increased TF activity, TF mRNA levels in adipocytes and adipose-infiltrating macrophages, and elevated plasma TAT levels. (▇▇▇▇▇ et al., 2008) Visceral adipose tissue is metabolically active, producing pro-angiogenic and pro-inflammatory cytokines and hormone-like substances, which stimulate endothelial vasculature development within the adipose tissue, acting as a phospholipid surface for the initiation and propagation of the coagulation cascade. (▇▇▇▇▇▇▇ et al., 2007) These cytokines and hormone-like substances also act as activators for the coagulation cascade, and attract and activate platelets. (▇▇▇▇▇▇▇ et al., 2007) Obesity is associated with platelet activation and increased mean platelet volume, platelet microparticles, thromboxane B2 metabolites, soluble P-selectin, and platelet derived CD40L. (▇▇▇▇▇▇▇▇ & Tenno, 2000) Obesity is considered to be a low-level inflammatory state, which amplifies thrombosis both directly, via cytokines and indirectly, via oxidative stress. (▇▇▇▇▇▇▇ et al., 2007; ▇▇▇▇▇▇▇ et al., 2007) Interleukein-6 (IL-6) is a cytokine produced in adipose tissues, as well as in immune cells. Its level increases in association with increasing...