Gene expression of adipose tissue, endothelial cells and platelets in subjects with metabolic syndrome (Review).

Metabolic syndrome is a combination of medical disorders including hypertension, dyslipidemia, hyperglycemia, insulin resistance and increased waist circumference, and is associated with a higher risk of cardiovascular disease. An increase in adipose tissue mass is associated with the augmented secretion of certain adipokines, such as interleukin-6, tumor necrosis factor-α and resistin, which cause endothelial dysfunction (an increase in vasoconstrictor molecules and in the expression of adhesion molecules as well as a decrease of vasodilator molecules, amongst other features) and hemostasis alterations that also favor a prothrombotic state (increased fibrinogen and plasminogen activator inhibitor-1 concentrations and platelet activation/aggregation). This interaction between adipose tissue, endothelial cells and platelets is associated with an increase or decrease in the expression of several transcription factors (peroxisome proliferator-activated receptors, CCAAT-enhancer-binding proteins, carbohydrate responsive element-binding proteins and sterol regulatory element-binding proteins) that play a crucial role in the regulation of distinct metabolic pathways related to the metabolic syndrome. In the present review, we present the primary changes in adipose tissue, endothelial cells and platelets in subjects with metabolic syndrome and their possible target sites at the gene expression level.

Increased concentration of plasminogen activator inhibitor-1 and fibrinogen in individuals with metabolic syndrome.

Metabolic syndrome (MS) is closely linked to a generalized metabolic disorder referred to as insulin resistance. Disturbances in the hemostasis and fibrinolytic systems are a feature of MS. The aim of this study was to determine the concentration levels of fibrinogen and plasminogen activator inhibitor-1 (PAI-1) in a group of patients with MS with respect to a non-MS group, and to evaluate their possible relation with other risk factors in MS. The study was carried out in a total of 186 male and female non-smoking individuals aged 45-64 years, 93 with MS (ATP III criteria) and 93 without MS. Plasmatic levels of PAI-1 were measured by ELISA, and those of fibrinogen by the Claus method. The plasmatic levels of PAI-1 (men 49.2±19.8 vs. 35.0±12.2 ng/ml and women 42.0±19.7 vs. 31.6±14.6 ng/ml; p=0.0026) and fibrinogen (274.0±82.1 vs. 232.7±66.6 ng/ml; p=0.0002) were significantly higher in the MS group than in the non-MS group. PAI-1 was significantly associated with diastolic blood pressure, triglycerides and waist circumference. Fibrinogen was negatively associated with HDL-c. High plasmatic levels of PAI-1 and fibrinogen contribute to the cardiovascular risk that characterizes individuals with MS.

Increased concentrations of soluble vascular cell adhesion molecule-1 and soluble CD40L in subjects with metabolic syndrome.

Metabolic syndrome (MS) is associated with a high incidence rate of cardiovascular disease. It is characterized by abdominal obesity, elevated blood pressure, atherogenic dyslipidemia [high LDL-c (low density lipoprotein cholesterol) and low HDL-c (high density lipoprotein cholesterol)] and insulin resistance or glucose intolerance. In the context of MS, alterations in the plasmatic levels of some soluble forms of cell adhesion molecules can appear, e.g., soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin) and soluble CD40L (sCD40L). The objective of this study was to compare the serum levels of sVCAM-1, sE-selectin and sCD40L in MS and non-MS groups and to associate these molecules with the diagnostic criteria of MS. A total of 185 non-smokers between 45 and 64 years of age were included. Of these, 93 corresponded to the MS group and the remaining 92 to a non-MS group (according to modified ATP III criteria). The serum concentration of sVCAM-1, sE-selectin and sCD40L was determined by commercial solid phase ELISA. The results were expressed as a median and interquartile range. The MS group showed high levels of sVCAM-1 (558.9 ng/ml; 481.3-667.6 ng/ml) compared with the non-MS group (405.2 ng/ml; 361.0-470.5 ng/ml) (p<0.0001). As well, the median level of sCD40L (3.0 ng/ml; 2.1l-11.7 ng/ml) was significantly higher in the MS group than that in the non-MS group (2.6 ng/ml; 2.3-3.4 ng/ml) (p=0.0061). sE-selectin levels did not differ significantly between the groups: 73.9 ng/ml (58.3-87.0 ng/ml) and 68.5 ng/ml (51.6-97.5 ng/ml) in the MS and non-MS group, respectively. In conclusion, the serum levels of sVCAM-1 and sCD40L, but not sE-selectin, were significantly higher in patients with MS than in subjects that did not present MS. MS may therefore increase the expression of cell adhesion molecules, probably through endothelial activation.

An insight into the pathophysiology of thrombosis in antiphospholipid syndrome.

The antiphospholipid syndrome (APS) is a disorder which is characterized by the presence of autoimmune antiphospholipid antibodies (APL) and increased risk of thrombosis and fetal loss. APL are associated with recurrent abortions in APS patients and participate in the pathogenesis of venous or arterial thrombosis, although the underlying mechanisms are poorly understood. Antigens that are targeted by APL include beta 2 glycoprotein I and prothrombin. Pathological mechanisms of APL encompass inhibition of natural anticoagulants (protein C system, tissue factor pathway inhibitor, and annexin A5), inhibition of the fibrinolytic system, activation of endothelial cells, monocytes and platelets, and complement activation. In this review, we discuss the main targets of APL and prothrombogenic mechanisms of APL.

Prevalence of antiphospholipid antibodies is not different in Chilean diabetic patients and normal individuals.

Diabetes mellitus (DM) is complicated by vascular and neurological events. Antiphospholipid (aPL) antibodies have already been associated with many clinical conditions, including venous and arterial thrombosis, as well as recurrent fetal loss. However, a significant association between aPL antibodies and DM has not been widely reported yet. In the present study, we investigated the prevalence of aPL antibodies in diabetic patients. This study included 100 Chilean diabetic patients (67 of them with some complications and 33 without complications; 28 with Type 1 and 72 with Type 2 DM) and 100 healthy blood donor controls. Each sample was analyzed for IgG, IgM and IgA anticardiolipin (aCL), anti-beta(2) glycoprotein I (anti-beta(2)GPI), antiprothrombin (aPT) antibodies, and lupus anticoagulant (LA). Fourteen out of 100 (14%) diabetic patients presented some type of aPL antibodies. Four patients were positive for aCL antibodies, two for anti-beta(2)GPI antibodies, and nine for aPT antibodies. All patients were LA negative. The incidence of different isotypes was similar in each of the aPL antibodies studied, and their activities were low. No significant correlation was observed between aPL antibodies and vascular complications.