A preliminary evaluation of VEGF-A, VEGFR1 and VEGFR2 in patients with well-controlled type 2 diabetes mellitus

Objective： Decompensated chronic hyperglycemia often leads to late microvascular complications such as retinopathy, diabetic foot syndrome, and diabetic kidney disease. The aim of this study was to determine the concentration of vascular endothelial growth factor A （VEGF-A） and its receptors in patients with well-controlled diabetes. Methods： The study was conducted on 31 patients with well-controlled type 2 diabetes without microor macroangiopathy. Thirty healthy volunteers were enrolled in a control group. Serum concentrations of VEGF-A, VEGF receptors 1 and 2 （VEGFR1 and VEGFR2）, fasting glucose, and lipid profiles were measured, and the plasma concentration of glycated hemoglobin （HbAlc） was determined. Results： No significant differences were observed between the concentration of VEGF-A, VEGFR1 or VEGFR2 in the subject group and that in the control group. Positive correlations were noted between the levels of VEGF-A, VEGFR2, and triglyceride, and there was a negative correlation between the levels of VEGFR2 and high-density lipoprotein （HDL）-cholesterel in the study group. Conclusions： The concentrations of VEGF-A and its receptors 1 and 2 in patients with well-controlled diabetes are comparable to those of healthy individuals, which may indicate that appropriate control of glucose levels delays the occurrence of vascular complications. A negative correlation between VEGFR2 and HDL-cholesterol levels, and positive correlations between VEGF-A, VEGFR2, and triglyceride levels, suggest that lipid abnormalities occurring in diabetes may be involved in the modulation of angiogenesis.

Overweight and obesity versus concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 in plasma of patients with lower limb chronic ischemia

Objective： Being overweight or obese comprises a significant risk factor for atherosclerosis. Fat tissue also generates factors stimulating angiogenesis, the process by which new blood vessels form. The purpose of this paper is to assess concentrations of the vascular endothelial growth factor A （VEGF-A） and its soluble type-1 and type-2 re- ceptors （sVEGFR-1 and sVEGFR-2） in plasma of patients with peripheral arterial disease （PAD） depending on the level of nutrition according to body mass index （BMI）. Methods： The study group included patients suffering from symptomatic PAD （n=46） in Fontaine classes Ila-lV without any history of neoplastic disease and who have a normal BMI （n=15）, are overweight （n=21） or are obese （n=10）. The control group （n=30） consisted of healthy non-smoking volunteers who were neither overweight nor obese. Venous blood plasma samples were collected from both groups at rest in the morning to determine plasma concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 using the enzyme- linked immunosorbent assay （ELISA） method. Results： The group of patients with PAD co-existent with being over- weight or obese tended to have higher mean concentration levels of VEGF-A and sVEGFR-2 when compared with patients suffering from PAD with normal BMIo A statistically significant positive correlation was obtained between BMI and average plasma concentrations of sVEGFR-2 （R=0.37, P=-0.0103）. However, no significant correlation was no- ticed between BMI and VEGF-A or sVEGFR-1 concentrations. Conclusions： A positive correlation determined be- tween the level of antiangiogenic factor and BMI value may be indicative of the linearly growing prevalence of some antiangiogenic factors in patients with metabolic disorders, which may be one of numerous factors contributing to incomplete efficiency of collateral circulation development in patients with PAD.

Effect of uncontrolled hyperglycemia on levels of adhesion molecules in patients with diabetes mellitus type 2

Objective： Uncontrol ed diabetes has become a major cause of mortality and morbidity by reason of vascular angiopathy. The aim of this study was to evaluate the concentrations of soluble forms of vascular adhesion molecule-1 （sVCAM-1）, intercel ular adhesion molecule-1 （sICAM-1）, E-selectin, and thrombomodulin in patients with wel-control ed and uncontrol ed diabetes type 2. Methods： The study was conducted on 62 patients with diabetes. Group I consisted of 35 patients with wel-control ed diabetes. The second group included 27 patients with uncontrol ed diabetes with micro-albuminuria. A control group was made up of 25 healthy volunteers. The concentrations of sVCAM-1, sICAM-1, sE-selectin, and soluble thrombomodulin were assayed in plasma. Serum concentration of cre-atinine was measured and the plasma concentrations of fasting glucose and glycated hemoglobin （HbA1c） determined. Results： Lower concentrations of ICAM-1 were found in the group of uncontrolled diabetes patients compared with those with wel-control ed disease. In patients with uncontrol ed diabetes, VCAM-1 levels were significantly higher compared with the group with wel-control ed diabetes. In patients with uncontrol ed diabetes a positive correlation was obtained between glomerular filtration rate and sE-selectin and a negative correlation between the levels of creatinine and ICAM-1, although there was a positive correlation between （HbA1c） and ICAM-1. Conclusions： The study con-firmed the participation of the inflammatory process associated with impaired vascular endothelial function in the pathogenesis of type 2 diabetes. The opposite effect of uncontrolled hyperglycemia on adhesion molecules suggests different functions of VCAM-1 and ICAM-1 in complications of diabetes.

Risk of venous thromboembolic disease in postmenopausal women taking oral or transdermal hormone replacement therapy

Objective: The influence of hormone replacement therapy (HRT) on hemostasis processes depends on the type of hormone,the combination of doses,the time of taking HRT,and the route of administration (oral,transdermal,implanted).The aim of the current study was to assess some parameters of coagulation,especially tissue factor pathway inhibitor (TFPI) and tissue factor (TF) in postmenopausal women using oral or transdermal HRT.Methods: The study was conducted on 76 healthy women,including 46 women aged 44–58 years who were taking oral (26) or transdermal (20) HRT,and 30 women aged 44–54 years who did not take HRT as the control group.Plasma concentrations of TF,TFPI,thrombin-antithrombin complex (TAT),and D-dimer were performed by enzyme-linked immunosorbent assay (ELISA).Moreover,the concentration of fibrinogen and activity of protein C were measured by chromogenic and chronometric methods.Results: We observed a significantly higher concentration of TF and a significantly lower concentration of TFPI in women taking oral and transdermal HRT in comparison with the control group.We also found a significantly lower concentration of fibrinogen in women taking oral HRT vs.the control group.Moreover,no statistically significant changes in concentrations of TAT and D-dimer,or activity of protein C were noted.Conclusions: In this study,the occurrence of an increased TF concentration simultaneously with a decreased concentration of TFPI in women taking HRT indicates hypercoagulability.No significant modification of TAT or D-dimer occurred,and thus there may not be increased risk of thrombosis.