Hemostasis alterations in metabolic syndrome (Review)

Abstract

Abstract. Metabolic syndrome (MS) is characterized by the presence of at least three of the following alterations: enlargement of the waist diameter, higher levels of arterial pressure, low density lipoprotein cholesterol and glycemia, and reduction of high density lipoprotein cholesterol. The prevalence of MS reaches 23% in young adults, a percentage that increases with age. People with MS have a greater risk of suffering from cardiovascular disease (CVD). The physiopathologic alterations now found to exist in MS are diverse; among them is endothelial dysfunction, which triggers atherogenic lesions and hypercoagulability characterized by alterations of the coagulation factors and the regulatory proteins of fibrinolysis such as the plasminogen activator inhibitor (PAI-1). The increase in oxidative stress and/or the reactive oxygen species in patients with MS is partially related to the oxidation state of the lipoproteins, especially of the low density lipoproteins. This fact favors atherogenesis. Moreover, the oxidative stress produces alterations in the production of adipokines, cytokines secreted by the adipose tissues. The abnormality in the transport of lipoprotein diminishes the catabolism of the very low density lipoprotein (VLDL) and increases the catabolism of the high density lipoprotein (HDL), which creates insulin resistance. This process is associated with a lower concentration of adiponectin that in turn regulates the catabolism of VLDL and HDL; consequently increasing the flow of fatty acids from the adipose tissue to the liver and muscles. The proinflammatory cytokines, among them tumor necrosis factor · (TNF-·), are of great importance in MS regulating different processes and molecules such as PAI-1. PAI-1 is controlled by the group of transcription factors peroxisome proliferator-activated receptor (PPAR), especially by PPAR Á and · ligands. In summary, MS includes multiple alterations related to insulin resistance at several levels: hepatic, muscular, adipose and vascular tissue (endothelium). The exact mechanism that underlies the relationship between MS and CVD are not sufficiently known yet; pathogenic explanations are lacking for the mechanisms relating metabolic factors to insulin resistance and the association with the development of atherosclerosis and thrombosis. MS alterations and the main aspects related to homeostasis alterations are examined in this report.

Hemostatic abnormalities in endocrine and metabolic disorders

“…As recently reviewed by several investigators including our group (120)(121)(122)(123)(124)(125), the metabolic syndrome is frequently associated with a hypercoagulable condition, in that the coagulation system is switched toward a prothrombotic state, involving increased plasmatic coagulation, reduced fibrinolysis, decreased endothelial thromboresistance, and predominantly platelet hyperactivity. All of these abnormalities in the coagulation and fibrinolytic systems may contribute to the development of cardiovascular complications in patients with the metabolic syndrome.…”

“…Simultaneously, the presence of endothelial dysfunction and atherogenic dyslipidemia, mainly hypertriglyceridemia, may trigger platelet aggregation, thus further increasing the risk of thrombotic events (120,123,124,132,133). A disorder of triglyceride metabolism is a key feature in the metabolic syndrome, and there is now ample evidence supporting a strong association between hypertriglyceridemia and hypercoagulability (120)(121)(122)(123)(124)(125)135). In particular, the concentrations of very-low density lipoprotein (VLDL) and remnant lipoproteins are often increased in the metabolic syndrome, and they can trigger platelet activation and activate the coagulation pathway, supporting the assembly of the prothrombinase complex (120)(121)(122)(123)(124)(125)135).…”

Gamma-Glutamyl Transferase

“…These include parameters of obesity and products released by adipose tissue, plasma insulin levels and insulin-like growth factors, liver enzymes, C-reactive protein and circulating metabolites, several components of circulating lipoproteins, microalbuminuria, and markers of increased cellular inflammation. [51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] The status of these biomarkers as causative factors, either in generation of the metabolic syndrome or directly in atherogenesis, at present is uncertain. Some of them have been implicated as causes, but others as a reflection of a metabolic abnormality.…”

El Consumo De Frutas Y Hortalizas Ayuda a Prevenir El Daño Endotelial

“…Una característica común de la disfunción endotelial es la disminución de la biodisponibilidad de NO a nivel vascular (56), acompañada de otras alteraciones en el fenotipo endotelial que aumentan aún más la propensión a la vasoconstricción (57), trombosis, inflamación y a la proliferación celular en el lecho vascular (58)(59)(60)(61). La disfunción endotelial es el resultado de la presencia de FRCV y el desarrollo de aterosclerosis (62).…”