Figure 2.

Endothelial dysfunction is orchestrated by various mechanisms: metabolites, molecular and inflammatory. Hyperinsulinemia, CVD and vitamin D have a strong impact on homeostatic equilibrium. Both hyperinsulinemia and hyperglycaemia generate states of increased coagulation and decreased fibrinolysis. By driving the development of CVD, diabetes mellitus and obesity, they contribute to the inflammatory substrate of cytokines. They increase the ROS production due to the damage in decreasing both NAD+ and reduced glutathione (GSH). A reduction in vitamin D due to sequestration into the adipocytes induces lipogenesis with de-creased level of cathelicidin and cholecalciferol, leading to decreased levels of ChS and HSPG, regulators of RBCs deformation and increased cells agglutination. These mechanisms are all responsible for thrombosis initiation. The vascular inflammation and decreasing levels of Ch-S and HSPG are represented with coloured backgrounds being the main actors of thrombogenesis trigger. In addition, thrombogenesis, the main effect, is outlined with a different colour too. Abbreviations: Ch-S: cholesterol sulfate, CVD, cardiovascular disease; EDRFs, endothelium-derived relaxing factors, HSPG: heparan sulfate proteoglycans, NAD+: nicotinamide adenine dinucleotide, PAI-1 plasminogen activator inhibitor type 1, RBC, red blood cell; ROS: reactive oxygen species, T2DM: type 2 diabetes mellitus, SIRT3: sirtuin 3, TNF-α: tumour necrosis factor-α, IL-6: interleukin 6.