Endothelial Dysfunction In Group Research Articles

The Evaluation of Adropin and Autotaxin as Potential Markers of Endothelial Dysfunction in Preeclampsia.

Endothelial dysfunction (ED) plays a prominent role in the pathogenesis of preeclampsia (PE). There is a need for non-invasive methods to assess endothelial function in preeclamptic patients. In the present study, adropin, autotaxin (ATX), and lysophosphatidic acid (LPA) were evaluated as indicators of ED. Patients diagnosed with PE and healthy pregnant women (n = 42 for each group) were compared. After measuring flow-mediated dilation (FMD), the participants were stratified as ED (+) or ED (-) based on a cut-off value of 6.5%. The PE patients were divided as early/late onset PE and severe/mild PE. Adropin, ATX, and LPA levels were measured, and their relevance to ED was evaluated. Student t, Mann-Whitney U, or ANOVA tests were used for statistics, as appropriate. Adropin levels were diminished in the ED (+) group, whereas ATX and LPA levels were increased. The decrease in adropin levels was more pronounced in severe PE, showing a positive correlation with the FMD. In the logistic regression model, adropin was the only parameter that was an independent variable for the FMD test (P < .001). Adropin measurements in serum may be of value for disease follow-up in patients with PE.

Abstract 13745: Electronic Cigarette-Derived Aerosols Induce Endothelial Dysfunction: Role of Aldehydes and Transient Receptor Potential Ankyrin-1 in Mice

Introduction: Electronic cigarettes (e-cigs) threaten to reverse the decline in rates of nicotine dependence and smoking. While some believe that e-cigarettes are less harmful than combustible cigarettes, e-cig use is associated with respiratory symptoms (cough, wheeze) and endothelial dysfunction (ED) indicating a potential to increase the risk of cardiovascular disease (CVD) with chronic use. ED is sine qua non of multiple CVD, yet the mechanism of e-cig-induced ED is unknown. Hypothesis: E-cigs generate levels of irritants that activate the Transient Receptor Potential Ankyrin-1 (TRPA1) to trigger nocifensive reflexes and induce ED in mice. Methods: Wild type (WT) and TRPA1-null C57BL/6J male and female mice were exposed to: filtered air (control), aerosols of JUUL e-cig liquid, e-cig solvents without nicotine (propylene glycol:glycerin, PG:G), or irritant gases alone (acrolein, formaldehyde). Urinary levels of nicotine and aldehyde metabolites were measured by UPLC-MS/MS. During acute exposures, respiratory irritant responses were monitored by radiotelemetry. Following short-term exposure (4d), aortic endothelial function, blood/plasma markers of organ toxicity, and platelet activation were measured. Results: Exposure of WT mice to e-cig aerosols increased urine levels of the acrolein, but not formaldehyde, metabolite (3HPMA), to that of exposures to 1 ppm acrolein alone. In WT mice, exposure to either PG:G (30:70), formaldehyde (5 ppm), or acrolein (1 ppm) induced respiratory braking. In female WT mice (n=5-18), exposure to PG:G (-61.8±4.2 % ACh relaxation) and formaldehyde (–56.3 ± 4.5 %) but not acrolein (-80.0±3.2 %) induced ED vs control group (-77.8±1.5 %). In female TRPA1-null mice (n=5-14), neither PG:G (-77.6±3.6 %), formaldehyde (-85.9±7.8 %) nor acrolein (-86.6±2.8 %) exposure induced ED vs control (-81.3±5.4 %). Acrolein exposure enhanced aortic sensitivity to an NO donor similarly in female WT and TRPA1-null mice. Conclusions: Formaldehyde and acrolein generated from the PG:G in e-cigs provoked pulmonary irritant reflexes, and formaldehyde exposure alone induced ED in female mice. Irritant aldehydes in e-cig-derived aerosols activate the TRPA1 receptor to promote ED that could increase CVD risk.

COVID 19 disease independently predicted endothelial dysfunction measured by flow-mediated dilatation.

The systemic effects of COVID-19 disease are still largely uncertain and needs to be scrutinized with further trials. Endothelial dysfunction (ED) is responsible for the majority of adverse cardiovascular events. Flow-mediated dilation (FMD) is easily obtainable method to assess ED accurately. It is aimed to evaluate ED by measuring FMD following COVID-19 disease. Patients diagnosed with COVID-19 disease were recruited to the hospital two month after the discharge. Sex and age-matched healthy subjects were determined as the control group. Blood samples and FMD measurements were obtained from each participant. All subjects were divided into two groups according to the presence of ED determined by FMD measurements. These two groups were compared in terms of demographic features and the presence of recovered COVID-19 disease. A total of 92 subjects consisting of 59 without ED and 33 with ED were included in the study. ED (+) group was older (p = 0.015) and more likely to have hypertension (p = 0.044) and COVID-19 rate was higher in ED (+) group (p = 0.009). While neutrophil count (p = 0.047) and CRP (p = 0.036) were higher, eGFR (p = 0.044) was lower in ED (+) group. In the backward multivariable regression analysis, COVID-19 disease [OR = 3.611, 95% CI 1.069–12.198, p = 0.039] and BMI [OR = 1.122, 95% CI 1.023–1.231, p = 0.015] were independent predictors of ED. COVID-19 disease may cause ED which is the major underlying factor of cardiovascular diseases. Furthermore, COVID-19 disease may deteriorate the existing cardiovascular disease course. Detecting ED in the early phase or preventing by new treatment modalities may improve short and long-term outcome.

Effect of fructooligosaccharide on endothelial function in CKD patients: a randomized controlled trial.

Microbiota-derived uremic toxins have been associated with inflammation that could corroborate with endothelial dysfunction (ED) and increase cardiovascular risk in patients with chronic kidney disease (CKD). This trial aimed to evaluate the effect of the prebiotic fructooligosaccharide (FOS) on endothelial function and arterial stiffness in nondialysis CKD patients. In a double-blind controlled trial, 46 nondiabetic CKD patients were randomized to receive 12 g/day of FOS or placebo (maltodextrin) for 3 months. Total p-cresyl sulfate (PCS) and indoxyl sulfate by high-performance liquid chromatography, urinary trimethylamine N-oxide by mass spectrometry, C-reactive protein, interleukin-6 (IL-6), serum nitric oxide and stroma-derived factor-1 alfa were measured at baseline and at the end of follow-up; endothelial function was assessed through flow-mediated dilatation (FMD) and arterial stiffness by pulse wave velocity (PWV). The mean (± standard deviation) age of the study participants was 57.6 ± 14.4 years, with an estimated glomerular filtration rate of 21.3 ± 7.3 mL/min/1.73 m2. During the follow-up, regarding the inflammatory markers and uremic toxins, there was a significant decrease in IL-6 levels (3.4 ± 2.1 pg/mL versus 2.6 ± 1.4 pg/mL; P = 0.04) and a trend toward PCS reduction (55.4 ± 38.1 mg/L versus 43.1 ± 32.4 mg/L, P = 0.07) only in the prebiotic group. Comparing both groups, there was no difference in FMD and PWV. In an exploratory analysis, including a less severe ED group of patients (FMD ≥2.2% at baseline), FMD remained stable in the prebiotic group, while it decreased in the placebo group (group effect P = 0.135; time effect P = 0.012; interaction P = 0.002). The prebiotic FOS lowered circulating levels of IL-6 in CKD patients and preserved endothelial function only in those with less damaged endothelium. No effect of FOS in arterial stiffness was observed.

Функциональная активность эндотелия и иммунный статус при атеросклеротическом поражении аорто-подвздошного сегмента и реваскуляризации

Objective. The aim of the study is the evaluation of endothelial functional activity and immune status in systemic and local blood flow in atherosclerotic lesions of the aorto-iliac segment after open and endovascular interventions and establishing the relationship with the lesion class. Materials and methods. The study included 190 patients with lesions of the aorto-iliac segment. Depending on the type of surgical intervention, patients were divided into two groups: group I (n=97) - patients who underwent aorto-femoral bypass surgery, group II (n=93) - patients who underwent TRANS-balloon angioplasty with stenting of the iliac arteries. Results. Violations of the functional state of the endothelium and the immune status in the systemic and local blood flow, which do not correlate with the TASC II lesion class (TransAtlantic Inter-Society Consensus II), were revealed. There were differences in the factors of endothelial damage (in patients of group II before surgery, the level of homocysteine in the systemic blood flow, oxidized low-density lipoproteins in the systemic and local blood flow), hemostatic form of endothelial dysfunction (in group I, inhibitor of tissue plasminogen activator type I (PAI-1) in the systemic and tissue plasminogen activator (t-PA) in the local blood flow) and apoptosis (higher in group I in the systemic and local blood flow). During revascularization of the aorto-iliac segment, there were violations of the hemostatic form of endothelial dysfunction in group II with an increase in PAI-1 by 14.8% (p&lt;0.001) in the systemic blood flow and by 1.9 times (p&lt;0.001) in the revascularized arterial segment compared to group I. In group II after revascularization was significantly higher the immunoglobulins (Ig) class A in system and the circulating immune complexes, interleukins 1 (IL-1) in local blood flow and lower levels of IgM, interleukins 6 (IL-6), IL-1 in system and IgA, IgM, IL-6 in local blood flow compared with I group. Conclusion. The study of the features of the functional state of the endothelium and the immune status will optimize the management strategies of patients after various types of revascularization interventions on the aorto-iliac segment.

Association between lipid profile and endothelial dysfunction as assessed by the reactive hyperemia index

ABSTRACT Introduction We investigated the associations between endothelial dysfunction (ED) as evaluated by the reactive hyperemia index (RHI) obtained using Endo-PAT2000® and atherosclerotic risk factors in patients who underwent coronary artery angiography (CAG). Methods The subjects consisted of 191 patients who were clinically suspected to have CAD and underwent CAG, and in whom we could perform Endo-PAT2000®. We divided the patients into ED (RHI<1.67, n = 71) and non-ED (RHI≥1.67, n = 120) groups. Results The ED group was significantly older and showed a higher ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) (L/H) than the non-ED group. A multivariate logistic regression analysis was performed to examine the associations between the presence of ED and age, gender, and BMI in addition to L/H. Age [odds ratio (OR) = 1.03, p = .02] and L/H (OR = 1.64, p = .01) were identified as significant independent markers of the presence of ED. Next, we divided 122 patients with statin treatment into ED (n = 40) and non-ED (n = 82) groups. The ED group tended to have higher L/H and lower HDL-C than the non-ED group. HDL-C (OR = 0.95, p = .01) and age (OR = 1.05, p = .04) were identified as independent markers of the presence of ED. Conclusions L/H was an independent marker of the presence of ED in patients without dyslipidemia. In addition, among patients with statin treatment, HDL-C was an independent marker of the presence of ED.

Subclinical elevated B-type Natriuretic Peptide (BNP) indicates endothelial dysfunction contributing to hypoxia susceptibility in healthy individuals

AimsBaseline elevated B-type Natriuretic Peptide (BNP) has been found in high altitude pulmonary edema susceptible population. Exaggerated pulmonary vascular response to hypoxia may be related to endothelial dysfunction in hypoxia susceptible. We hypothesize that baseline BNP levels can predict hypoxia susceptibility in healthy individuals. Main methodsThe pulmonary vascular response to hypoxia was compared in 35 male healthy individuals divided into two groups based on BNP levels (Group 1 ≤ 15 and Group 2 > 15 pg/ml). Acute normobaric hypoxia was administered to both the groups, to confirm hypoxia susceptibility in Group 2. Key findingsUnlike Group 1, Group 2 had elevated post hypoxia BNP levels (26 vs 33.5 pg/ml, p = 0.002) while pulmonary artery pressure was comparable. A negative correlation with tissue oxygen consumption (delta pO2) and compartmental fluid shift was seen in Group 1 only. Endothelial dysfunction in Group 2 resulted in reduced vascular compliance leading to elevation of mean blood pressure on acute hypoxia exposure. BNP showed a positive correlation with endothelial dysfunction in Group 2 and has been linked to pre-diabetic disorder (HbA1c 6 ± 0.44%) and may additionally represent a lower cross-sectional area of vascular bed related to vascular remodeling mediated by chronic hypoxia. SignificanceHypoxia susceptibility in healthy individuals may be related to endothelial dysfunction that limits vascular compliance during hypoxic stress. BNP level showed positive correlation with HbA1c (r = 0.49, p = 0.04) and negative correlation with delta pO2 (r = −0.52, p = 0.04) can predict reduced microvascular compliance due to endothelial dysfunction contributing to hypoxia susceptibility in healthy individuals. BNP levels≤15 pg/ml at sea level is indicative of hypoxia resistance.

The relationship between epicardial adipose tissue and endothelial dysfunction in patients with type 2 diabetes mellitus

Epicardial adipose tissue (EAT) has been shown to be related to cardiovascular risk. The aim of the present study was to investigate the relationship between EAT and endothelial function in patients with type 2 diabetes mellitus (DM). Type 2 DM patients were divided into two groups according to their brachial flow-mediated dilatation (FMD) values. The endothelial dysfunction (ED) group consisted of 46 patients with FMD change of <7%, while 46 patients with FMD change of >7% were accepted as the non-ED group. EAT thickness was measured on the right ventricular free wall from the transthoracic echocardiographic parasternal long- and short-axis views. The patients' demographic, anthropometric and laboratory findings were recorded. The mean diameter of EAT was 8.0±1.8 cm in the ED group and 6.6±1.2 cm in the non-ED group (p<0.001). The HbA1c levels were significantly higher in the ED group than non-ED group (8.55 [7.30-9.80], 7.45 [6.50-9.30], respectively; p=0.042). There were a negative correlation between FMD values and EAT (r=-0.437, p<0.001). The FMD values were weakly and negatively correlated with DM duration and HbA1c levels (r=-0.216, p=0.038; r=-0.266, p=0.010, respectively). EAT thickness was strongly correlated with body mass index (BMI) and waist length (r=0.405, p<0.001; r=0.515, p<0.001, respectively). The neutrophil count was significantly higher in the ED group than in the non-ED group. In multivariate logistic regression analysis, HbA1c and EAT diameters were found as predictors of ED in type 2 DM (odds ratio (OR): 1.887, 95% confidence interval (CI): 1.298-2.743, p=0.001; OR: 1.485, 95% CI: 1.054-2.093). EAT thickness predicts ED in patients with type 2 DM.

Evaluation of Oxidative Stress in Type 2 Diabetes Mellitus and Follow-up Along with Vitamin E Supplementation.

Increased oxidative stress is a widely accepted participant in the development and progression of diabetes and its complications. The present study has been undertaken to evaluate oxidative stress in type 2 diabetes mellitus and effect of vitamin E supplementation on oxidative stress. In all 120 subjects were enrolled in the present study, 40 subjects are age and sex matched controls. Test group comprised of clinically diagnosed (n = 80) type 2 diabetic patients. Biochemical parameters like serum MDA, nitric oxide, superoxide dismutase, erythrocyte reduced glutathione and platelet aggregation were analyzed in control and diabetic group. Test group is further categorized as Group I (n = 40) diabetics were treated by only hypoglycemic drugs and Group II (n = 40) diabetics were treated by hypoglycemic drugs with vitamin E supplementation. All above biochemical parameters were again reassessed after 3 months follow-up in both group and its values were compared with its respective baseline levels. The study shows, reduction of oxidative stress, improvement in antioxidant enzymes and endothelial dysfunction in group II, those were on treatment of hypoglycemic drugs along with vitamin E supplementation. Hence the present study may conclude that vitamin E supplementation along with hypoglycemic drugs may be beneficial to type 2 DM patients to minimize vascular complications.

ENDOTHELIAL DYSFUNCTION AND BLOOD PRESSURE VARIABILITY IN NORMOTENSIVE ADOLESCENTS: PP.6.244

Objective: To study the blood pressure (BP) variability (BPV) in normotensive adolescents with endothelial dysfunction (ED). Methods: It was conducted a prospective and transversal study, including 134 subjects (age: 15 ± 1.6 years), males (n = 63) and females (n = 71), normotensives, and free of cardiovascular disease. All subjects underwent 24-h ambulatory BP monitoring and endothelium-dependent flow-mediated dilation (FMD) in the brachial artery by high resolution ultrsonography. The systolic and diastolic BPV for 24-hour, day and night were expressed as the standard deviation of the obtained values. The presence of ED was defined as FMD less or equal to 10%. The variance ratio test (F-test) was applied to compare the BPV between the ED and normal endothelial function (NEF). Results: The ED prevalence was 23.9% (n = 32) in all adolescents, 53.1% (n = 17) in males and 46.9% (n = 15) in females (P:NS). Adolescents with ED showed significant higher nocturnal systolic and diastolic BPV than those with NEF, these values were (systolic BPV/diastolic BPV): 11.25/9.81 mmHg for ED and 10.22/8.50 mmHg for NEF (P < 0.01). The analysis by gender showed higher nocturnal BPV in males with ED than males with NEF (11.84/11.11 mmHg and 9.92/8.59 mmHg, respectively; P < 0.01), but the females did not show any significant differences. On the other hand, within the ED group, 24-h, diurnal and nocturnal systolic BPV was higher in males than females (11.09, 10.61, and 11.84 mmHg, and. 10.19, 9.97 and 9.17 mmHg, respectively; P < 0.01). Conclusions: There is a high ED prevalence in adolescents. In this age group, only nocturnal BPV is associated with the presence of ED. According to this study, the gender male with ED has abnormal systolic BPV levels. These conditions, ED and higher nocturnal BPV, are extremely important because from the early age the subjects could be in cardiovascular risk even they should be considered as healthy.

The relationships between post-prandial lipaemia, endothelial function and oxidative stress in healthy individuals and patients with type 2 diabetes

Post-prandial lipaemia (PPL) is a factor in atherogenesis and results in reversible endothelial dysfunction in healthy individuals. Oxidative stress and triglyceride (TG)-rich lipoproteins have been implicated. Type 2 diabetes (NIDDM) results in exaggerated PPL. We attempted to delineate the mechanisms of PPL induced, endothelial dysfunction (EF) and oxidative stress in 12 NIDDM and 12 matched healthy subjects. Subjects underwent a fat tolerance test, with endothelial function assessed by flow-mediated vasodilatation and oxidative stress measured by venous lipid-derived free radicals ex vivo and lipid peroxidation products over the postprandial phase. Fasting TG, post-prandial hypertriglyceridaemia and the TG enrichment of all lipoproteins was significantly greater in NIDDM. Post-prandial endothelial function inversely correlated with fasting HDL-C ( r=−0.84, P=0.001) in both the control and NIDDM groups. The deterioration in EF in the NIDDM group also correlated with TG enrichment of VLDL and LDL. PPL in both groups also resulted in increased oxidative stress. The increment in free radicals correlated with TG enrichment of VLDL in both groups and was, therefore, greater in NIDDM. Thus, PPL — with the production of TG-enrichment of VLDL — results in endothelial dysfunction by an oxidative stress mechanism in both groups. The magnitude is greater in NIDDM. Fasting HDL-C appears to contribute to the protection of the endothelium against this phenomenon. Hence, exaggerated PPL associated with reduced HDL-C may be important in the pathogenesis of vascular disease, particularly in NIDDM.