Endothelial Dysfunction Parameters Research Articles

Specific features of arterial stiffness and endothelial vasomotor dysfunction in patients with joint hypermobility syndrome

Introduction. Joint hypermobility syndrome (JHS) is characterized by a multisystem lesion of organs, including the cardiovascular system, which determines the presence of cardiovascular risks in this pathology. Aim. Studying of arterial stiffness and endothelial dysfunction parameters in patients with JHS. Material and methods. Study population included 105 adults with JHS (90 women and 15 men) and 57 healthy controls (49 women and 8 men) aged 20 to 28 years (mean age 22 [21; 23] years). All persons underwent a general clinical examination; examination of endothelial vasomotor function (EVF) and pulse wave velocity at the carotid-radial segment (PWVcr) by rheography (IMPECARD-M, Belarus); investigation of arterial stiffness parameters: cardio-ankle vascular index (CAVI), cardio-ankle pulse wave velocity (PWVha), ankle-brachial index (ABI), augmentation index (AI) by sphygmography (VaSeraVS-1500N Fukuda Denshi, Japan); determination of T786C polymorphism of the eNOS gene by polymerase chain reaction (Litech, Russia), determination of endothelin-1 and transforming growth factor beta-1 (TGF-β1) levels by enzyme immunoassay (Fine Test, Wuhan Fine Biotech Co., China). Results. According to the main clinical and laboratory indicators, the groups were matched. In patients with JHS, the values of PWV at the carotid-radial and cardio-ankle segments were higher, in other parameters (EVF, CAVI, ABI, AI) the groups were matched. In the group with JHS, pathological values of EVF, PWVcr, CAVI, AI were more often determined. Among patients with JHS, an excess of vascular age over the passport age is detected 8.6 times more often (95% CI from 1.103 to 67.321). These changes are not associated with mutations of the eNOS T786C gene and changes in endothelin-1 and TGF-β1 concentrations. Conclusion. These data indicate the importance of further study of the mechanisms of early vascular changes in the arteries in JHS, in order to develop optimal methods of therapy and improve the cardiovascular prognosis of patients with this pathology

A Comprehensive Analysis of Renal and Endothelium Dysfunction Markers Fourteen Years after Hemorrhagic Fever with Renal Syndrome Contraction.

While the pathology of acute hemorrhagic fever with renal syndrome (HFRS) has been widely researched, details on the chronic HFRS sequelae remain mainly unexplored. In this study, we analyzed the clinical and laboratory characteristics of 30 convalescent HFRS patients 14 years after the disease contraction, mainly emphasizing several endothelial dysfunction parameters. Convalescent HFRS patients exhibited significantly higher serum levels of erythrocyte sedimentation rate, von Willebrand factor, uric acid, C-reactive protein and immunoglobulin A when compared to healthy individuals. Furthermore, 24 h urine analyses revealed significantly lower sodium and potassium urine levels, as well as significantly higher proteinuria, microalbumin levels and β2-microglobulin levels when compared to healthy individuals. First morning urine analysis revealed significantly higher levels of hematuria in convalescent HFRS patients. None of the additional analyzed endothelium dysfunction markers were significantly different in post-HFRS patients and healthy individuals, including serum and urine P-selectin, E-selectin, soluble intercellular adhesion molecule 1, vascular intercellular adhesion molecule 1 (sVCAM-1) and vascular endothelial growth factor (VEGF). However, binary logistic regression revealed a weak association of serum sVCAM-1 and urine VEGF levels with HFRS contraction. Generally, our findings suggest mild chronic inflammation and renal dysfunction levels in convalescent HFRS patients 14 years after the disease contraction.

Laboratory indicators of hemostasis, lipid metabolism and endothelial dysfunction in men aged 18–50 years with different subtypes of ischemic stroke

Objective: to evaluate laboratory parameters of hemostasis, lipid metabolism and endothelial dysfunction and their relationship in men aged 18–50 years with atherothrombotic (ATS), lacunar (LS) and cardioembolic (CES) stroke. Material and methods. The study included 89 men with ATS (n=36), LS (n=34) and CES (n=19). Neuroimaging, ultrasound and laboratory blood serum analyses were performed in all patients. Results. The mean age of the patients was 42.6±5.3 years. The main risk factors for ATS, LS and CES included: arterial hypertension (75; 97.8 and 73.7% of cases, respectively), dyslipidemia (60; 41.3 and 42.1%), tobacco smoking (71.7; 67.4 and 52.6%), regular alcohol consumption (35; 19.6 and 36.8%), obesity (23.3; 8.7 and 15.8 %), diabetes mellitus (8.3; 6.5 and 10.5 %). Lower tissue plasminogen activator levels were found in patients with CES (2.66±1.77 ng/ml) compared to patients with LS (3.38±3.0 ng/ml) and ATS (3.48±2.45 ng/ml). Plasminogen activator inhibitor-1 levels were significantly increased in all stroke subtypes. The mean level of soluble thrombomodulin was highest in patients with LS (100.86±58.22 pg/ml) compared to patients with ATS (96.37±85.71 pg/ml) and CES (75.28±39.36 pg/ml). The level of asymmetric dimethylarginine was higher in patients with ATS (1.46±0.42 μmol/l) and in patients with LS (0.79±0.37 μmol/l), and in patients with CES (0.4±0.13 μmol/l) it was within the reference values. Conclusion. We noted differences in laboratory parameters of the hemostasis, lipid metabolism and endothelial dysfunction in men aged 18–50 years with different stroke subtypes (ATS, LS and CES), as well as clinical and laboratory correlations.

Strong Association of Metabolic Parameters with ADMA and VCAM-1 in Normo-Weight Subjects with Metabolic Syndrome.

Metabolic syndrome (MetS) is a risk factor for cardiovascular disease and is linked to obesity. Subjects with MetS who have normo-weight potentially show higher mortality and morbidity. This study aims to reveal the critical essential metabolic parameters associated with endothelial dysfunction in MetS subjects with normo-weight compared to obese. The study was designed using a case-control approach. Ninety-nine MetS subjects (34 Normo-weight and 65 obese) from the urban population were enrolled in this study. The components of MetS are based on NCEP/ATP III criteria. Asymmetric dimethylarginine (ADMA) and vascular cell adhesion molecule 1 (VCAM-1) as markers for endothelial dysfunction were measured in both groups. Fasting blood glucose (FBG) levels were higher in the normo-weight group (143.38 ± 79.8 mg/dL) compared to the obese group (120.89 ± 46.5 mg/dL). High-density lipoprotein cholesterol (HDL-c) levels in the normo-weight group were lower (42.82 ± 10.1 mg/dL) compared to obesity (45.74 ± 9.3 mg/dL), while triacylglycerol (TAG) levels were higher in the obese (197.25 ± 110.5 mg/dL) compared to the normo-weight group (167.03 ± 98.4 mg/dL), although the differences were statistically not significant (all p > 0.05). The difference between ADMA and VCAM-1 levels was statistically not significant in both groups. Correlation between MetS components with endothelial dysfunction parameters shows that metabolic parameters correlate strongly. Interestingly, a stronger correlation between FBG and ADMA was observed in normo-weight (r = 0.519) compared to obese groups (r = 0.445). In addition, TAG consistently shows a significant correlation with ADMA and VCAM-1 in normo-weight groups. Metabolic parameters, especially FBG and TAG, correlate strongly with endothelial dysfunction parameters in normo-weight subjects with metabolic syndrome.

EGCG, a Green Tea Compound, Increases NO Production and Has Antioxidant Action in a Static and Shear Stress In Vitro Model of Preeclampsia.

Preeclampsia (PE) is a gestational hypertensive disease characterized by endothelial dysfunction. Epigallocatechin-3-gallate (EGCG), the main compound in green tea, is a promising therapeutic target for the disease. By activating eNOS, EGCG increased NO production and exerted an important antioxidant action, but its specific impact in the context of PE remains understudied. The aim of this study is to evaluate the effects of EGCG on endothelial function in static and shear stress in in vitro models of PE. Endothelial cells were incubated with healthy (HP) and preeclamptic (PE) pregnant women's plasma, and the latter group was treated with EGCG. Additionally, NOS (L-NAME) and PI3K protein (LY249002) inhibitors were also used. The levels of NO, ROS, and O2•- were evaluated, as well as the antioxidant potential. These investigations were also carried out in a shear stress model. We found that EGCG increases the NO levels, which were reduced in the PE group. This effect was attenuated with the use of L-NAME and LY249002. Furthermore, EGCG increased the antioxidant capacity of PE, but its action decreased with LY294002. In cells subjected to shear stress, EGCG increased nitrite levels in the PE group and maintained its action on the antioxidant capacity. This is the first study of the effects of EGCG in this experimental model, as well as the investigation of its effects along with shear stress. Our findings suggest that EGCG improves parameters of endothelial dysfunction in vitro, making it a promising target in the search for treatments for the disease.

Association of clinical, imaging and laboratory parameters with adverse effects of glucocorticoid therapy in patients with giant cell arteritis.

Giant cell arteritis (GCA) is characterized by inflammation of large and medium vessels. First-line therapy for the treatment of GCA are glucocorticoids, which are effective while potential adverse effects should be considered, especially during long-term use. The aim was to investigate the incidence of glucocorticoids' adverse effects and potential predictors for them. 138 GCA patients were retrospectively evaluated for newly developed glucocorticoid adverse effects in 2020. Potential predictors, defined as initial glucocorticoid pulse therapy, relapse of GCA and concomitant polymyalgia rheumatica as well as parameters of inflammation and endothelial dysfunction, including pulse-wave velocity and intima-media-thickness, were measured in 2012. Potential new glucocorticoid adverse effects per patient was 1 (25th-75th 0-3) of which chronic kidney disease progression (29%), bone fractures (23.2%), cataracts (18.1%), dementia, and arterial hypertension (each at 12.3%) were most commonly recorded. Significant associations were found between occurrence of any relapse and new diabetes mellitus and between initial glucocorticoid pulse therapy and new dementia (all with p < 0.05). In multivariate regression analysis, any relapse was a predictor for developing diabetes mellitus (OR 9.23 [95% CI 1.33-64.05], p = 0.025). However, no correlations were observed between endothelial dysfunction or inflammatory parameters and development of new glucocorticoid adverse effects. GCA relapses may be associated for development of diabetes mellitus potentially by increasing glucocorticoid doses. Parameters of inflammation and endothelial dysfunction are not suited predictors for glucocorticoid adverse effects.

Possibilities of dapagliflozin-induced cardioprotection on doxorubicin + cyclophosphamide mode of chemotherapy-induced cardiomyopathy

RationaleThe global burden of cardiovascular (CV) and oncological diseases continues to increase. In this regard, the prevention of CV diseases (CVD) before and after cancer treatment is an urgent and unsolved problem in medicine. For this reason, our research group aimed to investigate the possibility of dapagliflozin-related cardioprotection, using an experimental model of chronic Doxorubicin (Adriamycin) + Cyclophosphamide (AC)-mode of chemotherapy-induced cardiomyopathy. ObjectiveThe redox balance, lipid metabolism, endothelial dysfunction, and myocardial damage parameters were measured to evaluate the pathways of dapagliflozin-induced stabilization of CV homeostasis. MethodsFor this study, 80 inbred Wistar rats were randomly assigned to four equally sized groups. A model of chronic cardiotoxicity was attained by using doxorubicin and cyclophosphamide co-administration. In the case, the markers of redox-balance, cholesterol metabolism, endothelial dysfunction, myocardial alteration, and morphological examination were assessed. ResultsFor all parameters, statistically significant deviations were obtained, emphasizing the sequel of AC-mode chemotherapy-related detergent effect on CV system (group 2). Moreover, the data obtained from dapagliflozin-treated groups (group 3) showed that this strategy provide limitation of lipid peroxidation, cholesterol metabolism and endothelial function normalization, with subsequent morphological preservation of myocardium. ConclusionDapagliflozin has a broad spectrum of pleiotropic influences, namely cholesterol-lowering, anti-inflammatory, and endothelium-stabilizing properties. These properties provide a favorable environment for the prevention of chemotherapy-related cardiomyopathy.

The Association Between Fluid Overload and Endothelial Dysfunction in Chronic Kidney Failure Patients Undergoing Hemodialysis Twice a Week.

Fluid overload causes excessive systemic vasoconstriction and decreased perfusion of peripheral tissues, leading to abnormalities in cardiopulmonary physiological functions. Prolonged fluid overload caused by inadequate hemodialysis may cause heart dilatation, left ventricular hypertrophy, hypertension, and a decrease in coronary reserves, which later will develop into coronary ischemia, leading to increased morbidity and mortality of cardiovascular disease (CVD). Endothelial dysfunction plays a role in excessive vasoconstriction on fluid overload. Brain natriuretic peptide (BNP) and asymmetric dimethylarginine (ADMA) are used as parameters of fluid overload and endothelial dysfunction, respectively. This study is conducted to describe the relationship between fluid overload with endothelial dysfunction. This study is a cross-sectional study of kidney failure patients who underwent hemodialysis twice weekly for at least three months. BNP and ADMA were used as parameters for fluid overload and taken prior to hemodialysis. From 126 subjects, the proportion with fluid overload (BNP>356 pg/ml) was found to be 64.3% with the median age of subjects being 52 years (47-62). There was 47.6% population with endothelial dysfunction (ADMA>100 ng/ml). Presumptive causes of primary chronic kidney disease (CKD) were hypertension (38.9%), diabetes mellitus (DM) (28.6%), and glomerulonephritis (21.4%). There was no significant association between fluid overload and endothelial dysfunction (PR=1,042, p=0.832 CI 95%=0.714-1.521). There was no relationship between fluid overload and endothelial dysfunction.

Changes in Adenosine Deaminase Activity and Endothelial Dysfunction after Mild Coronavirus Disease-2019.

Endothelial cells are a preferential target for SARS-CoV-2 infection. Previously, we have reported that vascular adenosine deaminase 1 (ADA1) may serve as a biomarker of endothelial activation and vascular inflammation, while ADA2 plays a critical role in monocyte and macrophage function. In this study, we investigated the activities of circulating ADA isoenzymes in patients 8 weeks after mild COVID-19 and related them to the parameters of inflammation and microvascular/endothelial function. Post-COVID patients revealed microvascular dysfunction associated with the changes in circulating parameters of endothelial dysfunction and inflammatory activation. Interestingly, serum total ADA and ADA2 activities were diminished in post-COVID patients, while ADA1 remained unchanged in comparison to healthy controls without a prior diagnosis of SARS-CoV-2 infection. While serum ADA1 activity tended to positively correspond with the parameters of endothelial activation and inflammation, sICAM-1 and TNFα, serum ADA2 activity correlated with IL-10. Simultaneously, post-COVID patients had lower circulating levels of ADA1-anchoring protein, CD26, that may serve as an alternative receptor for virus binding. This suggests that after the infection CD26 is rather maintained in cell-attached form, enabling ADA1 complexing. This study points to the possible role of ADA isoenzymes in cardiovascular complications after mild COVID-19.

Association of amino acids and parameters of bone metabolism with endothelial dysfunction and vasculopathic changes in limited systemic sclerosis.

Pathways contributing to endothelial dysfunction in patients with limited cutaneous systemic sclerosis (lcSSc) are largely unknown. The aim of this study was to investigate potential associations of amino acids and parameters of bone metabolism with endothelial dysfunction and vasculopathy-related changes in patients with lcSSc and early-stage vasculopathy. Amino acids, calciotropic parameters, including 25-hydroxyvitamin D and parathyroid hormone (PTH), and bone turnover parameters, including osteocalcin and N-terminal peptide of procollagen-3 (P3NP), were measured in 38 lcSSc patients and 38 controls. Endothelial dysfunction was assessed by biochemical parameters, pulse-wave analysis, flow-mediated and nitroglycerine-mediated dilation. Additionally, vasculopathy-related and SSc-specific clinical changes including capillaroscopic, skin, renal, pulmonary, gastrointestinal and periodontal parameters were recorded. No significant differences in amino acids, calciotropic and bone turnover parameters were observed between lcSSc patients and controls. In patients with lcSSc, several significant correlations were found between selected amino acids, parameters of endothelial dysfunction, vasculopathy-related and SSc-specific clinical changes (all with p < 0.05). In addition, significant correlations were observed between PTH and 25-hydroxyvitamin D with homoarginine, and between osteocalcin, PTH and P3NP with modified Rodnan skin score and selected periodontal parameters (all with p < 0.05). Vitamin D deficiency defined as 25-hydroxyvitamin D < 20 ng/ml was associated with the presence of puffy finger (p = 0.046) and early pattern (p = 0.040). Selected amino acids may affect endothelial function and may be associated to vasculopathy-related and clinical changes in lcSSc patients, while the association with parameters of bone metabolism seems to be minor.

Heart Rate from Progressive Volitional Cycling Test Is Associated with Endothelial Dysfunction Outcomes in Hypertensive Chilean Adults.

A progressive volitional cycling test is useful in determining exercise prescription in populations with cardiovascular and metabolic diseases. However, little is known about the association between heart rate during this test and endothelial dysfunction (EDys) parameters in hypertensive (HTN) patients. To investigate the association between EDys markers (flow-mediated dilation [FMD], pulse wave velocity of the brachial artery [PWVba], and carotid-intima media thickness [cIMT]) and heart rate during a cycling test in HTN adults. A secondary aim was to characterize cardiovascular, anthropometric, and body composition outcomes in this population. This was a descriptive clinical study in which adults (men and women) were assigned to one of three groups: HTN, elevated blood pressure (Ele), or a normotensive control group (CG), and completed a progressive cycling test. The primary outcomes were FMD, PWVba, cIMT, and heart rate (HR) at 25-50 watts (HR25-50), 50-100 watts (HR50-100), and 75-150 watts (HR75-150) of the Astrand test. Secondary outcomes included body mass index (BMI), waist circumference, body fat percentage (BF%), skeletal muscle mass (SMM), resting metabolic rate (RMR), and estimated body age, as measured by a bio-impedance digital scale. Analyses of the associations between FMD, PWV, and HR25-50, HR50-100, and HR75-150 watts revealed no significant association in the HTN, Ele, and CG groups. However, a significant association was found between cIMT and HR75-150 watts in the HTN group (R2 47.1, β -0.650, p = 0.038). There was also a significant trend (p = 0.047) towards increasing PWVba in the CG, Ele, and HTN groups. Heart rate during a progressive cycling test is associated with the EDys parameters cIMT in HTN patients, with particularly strong predictive capacity for vascular parameters in the second and third stages of the Astrand exercise test compared to normotensive control.

Evaluation of maternal serum SERPINC1, E-selectin, P-selectin, RBP4 and PP13 levels in pregnancies complicated with preeclampsia

Objective The aim of this study is to investigate whether Serpin clade C (SERPINC1), E-selectin, P-selectin, Placental protein 13 (PP13), and Retinol-binding protein-4 (RBP4) levels in maternal serum were associated with the presence of preeclampsia and to compare them with uncomplicated pregnancies. Methods This prospective study included 40 women with preeclampsia and 40 healthy pregnant women. An enzyme-linked immunosorbent assay kit was used to measure serum SERPINC1, E-selectin, P-selectin, PP13, and RBP4 levels. Results The preeclampsia group had significantly higher E-selectin and P-selectin levels than the control group. PP13 and SERPINC1 levels were also significantly lower than the control group. There was no significant difference in RBP4 levels. The receiver operating characteristic curve revealed the best cutoff values for the following: E-selectin >19.2 ng/mL, with 87.5% sensitivity and 95% specificity; P-selectin >5.1 ng/mL, with 97.5% sensitivity and 100% specificity; PP13 ≤ 107.03 pg/mL, with 72.5% sensitivity and 77.5% specificity; and SERPINC1 ≤ 87.76 ng/mL, with 100% sensitivity and 97.5% specificity. Conclusion In this study, the endothelial dysfunction parameters SERPINC1, PP13, E-selectin, and P-selectin were found to be associated with preeclampsia. Endothelial dysfunction biomarkers in maternal non-serum body fluids may differ. More research is needed, especially to determine the relationship between SERPINC1 and preeclampsia.

Cross-Sectional Association Between Body Fat Composition and Biomarkers of Inflammation and Endothelial Dysfunction in Children with Overweight/Obesity.

Childhood obesity is most prevalent nutritional disorder worldwide. Studies on clinical correlations between body fat (BF) composition, lipid profile, inflammatory biomarkers, and endothelial dysfunction (ED) parameters in children from United Arab Emirates (UAE) are limited. Therefore, we aimed to study obesity pattern in children and determine clinical correlations with biomarkers. Children (6-13 years) from different schools were divided into obese, overweight, and normal groups based upon Centers for Disease Control and Prevention weight-for-age centiles study (n=166). Anthropometric, BF composition, lipid profile, inflammatory, and ED biomarkers were determined and analyzed using SPSS software. The mean age and weight ± SD of participants were 10.6 ± 2.6 years and 48.2 ± 19.5 kg with 65% as overweight or obese. In normal, overweight, and obese group male were 40 (70.2%), 35 (67.3%), and 40 (70.2%) and female were 17 (29.8%), 17 (32.7%) and 17 (29.8%). There was significant difference in age (p<0.01), height (p< 0.01), weight (p< 0.01) among groups. Obesity markers (MCP-1, leptin, adiponectin) showed positive correlation with age, height, weight, WC, BF%, body fat mass (BFM), body muscle mass (BMM). A significant correlation (all p<0.01) of BMM with SBP (r=0.412), DBP (r=0.255), MCP-1 (r=0.558), adiponectin (r=0.635), hs-CRP (r=0.263), IL-6 (r=0.348), TNF-alpha (r=0.370), ICAM-1 (r=0.237), and VCAM-1 (r=0.343). The inflammatory markers (ICAM-1, VCAM-1) showed significant correlations with age, height, weight, WC, BF%, BFM, BMM. Leptin significantly (all p<0.01) correlated with age (r=0.470), height (r=0.423), weight (r=0.677), WC (r=0.606), BF (r=0.700), BFM (r=0.752), and BMM (r=0.524) and negatively correlated with TBW (r=-0.701). Adiponectin also showed a significant (all p<0.01) positive correlation with age, height, weight, WC, BF, BFM, and BMM. A strong association between BF composition, lipid profile, and inflammatory and ED biomarkers was observed in the study. Thus, immediate measures should be implemented to reduce risk of obesity and associated diseases.

The role of asymmetric dimethylarginine in endothelial dysfunction and abnormal nitric oxide metabolism in systemic sclerosis: results from a pilot study.

Systemic sclerosis (SSc) is characterized by generalized vasculopathy affecting mainly small vessels while macrovascular involvement is less investigated. The aim of this study was to examine associations between asymmetric dimethylarginine (ADMA) - a biomarker of atherosclerosis - and assessments of macrovascular endothelial function in patients with SSc. This was a cross-sectional study including consecutive SSc patients attending the Scleroderma Outpatient Clinic. ADMA measurement in serum samples was based on an enzyme immunoassay technique. Participants underwent blood pressure measurement according to 2018 ESC/ESH Guidelines, applanation tonometry for the evaluation of arterial stiffness, and carotid ultrasound for the measurement of the intima-media thickness (cIMT). Eighty-one Caucasians (82.3% female) SSc individuals with mean age 55.44 ± 13.4years were included in this analysis. The correlation analysis of ADMA levels (unadjusted and adjusted values) with functional and morphological parameters of atherosclerosis revealed no statistically significant associations. Subgroup analysis based on disease duration (≤ 4years), immunologic profile (SCL-70 and ACA antibodies), disease type (limited, diffuse), and inflammatory status (erythrocyte sedimentation rate [ESR] > 25mm/h and C-reactive protein [CRP] > 5mg/L) showed no associations, except from a significant positive correlation between ADMA levels and cΙΜΤmean (r = 0.370, p = 0.044) in individuals with early SSc. The results of the study suggest that ADMA may be related with accelerated atherosclerosis in early stages of the disease. However, the lack of association between other morphological and functional parameters of endothelial dysfunction may suggest that other regulators of nitric oxide metabolism may contribute to macrovascular injury in SSc in various phases of the disease. Key Points • ADMA is a biomarker of atherosclerosis and has been linked with microvascular complications of SSc. •ADMA was not correlated with morphological and functional parameters of atherosclerosis in the population of the study. •The demonstrated association between ADMA and cIMT in patients with early SSc may suggest a role of NO/ADMA pathway in the initiation of macrovascular injury in SSc.

Methods for Measurements of Oxidized LDL, Homocysteine and Nitric Oxide as Clinical Parameters of Oxidative Stress and Endothelial Dysfunction

Abstract: Timely and accurate evaluation of clinical parameters associated with endothelial dysfunction is critical in diagnosing and treating atherosclerosis, which represents a severe health problem, accounting for at least 30% of deaths globally. A critical early event in the pathogenesis of atherosclerosis is the oxidative modification of low-density lipoprotein [LDL]. Oxidized LDL [OxLDL] represents numerous changes in lipid and apolipoprotein B [apo B] fractions of LDLs generated by lipid peroxidation. Another critical indicator of perturbed vascular homeostasis is homocysteine [Hcy], an amino acid containing sulfhydryl-group, an intermediate methionine and cysteine biosynthesis product. The total level of Hcy in plasma correlates better than cholesterol with the risk of cardiovascular disease. In addition, nitric oxide [NO] plays an essential role in regulating vascular physiological homeostasis due to its involvement in intravascular free radical and oxidant reactions. Reduced NO decreases oxidative stress in the vascular wall, which reduces the rate of LDL oxidation and the expression of redox-sensitive genes involved in atherogenesis. Endothelial dysfunction is typically associated with increased levels of OxLDL, decreased nitric oxide [NO], and hyperhomocysteinemia. Thus, OxLDL, Hcy, and NO are representative parameters of oxidative stress and endothelial dysfunction. Considering the important role of oxLDL, Hcy and NO in oxidative stress, atherogenesis and accompanying endothelial dysfunction, the challenge of the present work was to systematically present available methods for reliable measurement of these parameters and assess their potential for the use in the clinical setting. Here we present a comprehensive overview of analytical methods for measuring OxLDL, HCy, and NO in biological samples and discuss their advantages and potential problems regarding their application in clinical settings.

Clinical Pediatric Exercise Laboratories, Reactive Balance, Sleep, and Muscle Stimulation Considerations

Clinical Pediatric Exercise Laboratories, Reactive Balance, Sleep, and Muscle Stimulation Considerations

Assessment of Cardiovascular Function in Childhood Leukemia Survivors: The Role of the Right Heart.

Childhood acute lymphoblastic leukemia (ALL) survivors who underwent chemotherapy with anthracyclines have an increased cardiovascular risk. The aim of the study was to evaluate left and right cardiac chamber performances and vascular endothelial function in childhood ALL survivors. Fifty-four ALL survivors and 37 healthy controls were enrolled. All patients underwent auxological evaluation, blood pressure measurements, biochemical parameters of endothelial dysfunction, flow-mediated dilatation (FMD) of the brachial artery, mean common carotid intima-media thickness (c-IMT), antero-posterior diameter of the infra-renal abdominal aorta (APAO), and echocardiographic assessment. The ALL subjects had significantly lower FMD (p = 0.0041), higher left (p = 0.0057) and right (p = 0.0021) echocardiographic/Doppler Tei index (the non-invasive index for combined systolic and diastolic ventricular function) as compared to controls. Tricuspid annular plane excursion (TAPSE) was 16.9 ± 1.2 mm vs. 24.5 ± 3.7 mm, p < 0.0001. Cumulative anthracycline doses were related to TAPSE (p < 0.001). The ALL survivors treated with anthracyclines demonstrated systo/diastolic alterations of the right ventricle and reduced endothelial function compared with healthy controls. The early recognition of subclinical cardiac and vascular impairment during follow up is of utmost importance for the cardiologist to implement strategies preventing overt cardiovascular disease considering the growing number of young adults cured after childhood ALL.

Increasing circulating ESM-1 and adhesion molecules are associated with earlystage atherosclerosis in OSA patients:A cross-sectional study

BackgroundThere are increasing evidences for a direct relationship between the vascular system and obstructive sleep apnea (OSA). The aim of this study was to investigate the relationship between circulating endothelial cell specific molecule-1 (ESM-1), adhesion molecules and subclinical atherosclerosis in patients with OSA. MethodsThis was a cross-sectional study in which 161 patients with OSA and 56 controls were recruited. Demographic data, biochemical and polysomnography parameters were collected. We used a powerful high-throughput Multiplex Immunobead Assay technique to simultaneously test plasm levels of ESM-1, P-selectin, E-selectin, L-selectin, inter-cellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Carotid intima-media thickness (CIMT) were measured as parameters of vascular endothelial dysfunction and early atherosclerosis. ResultsIncreasing circulating levels of ESM-1, P-selectin, E-selectin, L-selectin, ICAM-1 and VCAM-1 were found increased in patients with OSA (all P < 0.001). Furthermore, OSA patients exhibited increased CIMT than controls (P < 0.05). Multivariate linear analysis indicated that elevated ESM-1, P-Selectin, E-selectin, and L-selectin levels were associated with AHI (all P < 0.05). Moreover, multivariate analysis showed that increasing ESM-1, VCAM-1, P-Selectin, and L-selectin were significantly associated with thick CIMT in OSA patients (all P < 0.05). ConclusionsIncreased circulating ESM-1 and adhesion molecules associated with thick CIMT in OSA, which is a marker of subclinical atherosclerosis. Strict attention to monitor circulating ESM-1 and adhesion molecules is necessary for early detection of subclinical atherosclerosis in OSA patients.

CARDIOVASCULAR RISK MARKERS IN PATIENTS WITH STRUCTURAL AND NUMERIC ABERRATIONS OF X CHROMOSOME

Objective: To assess the relationship between RAS, karyotype and cardiovascular risk factors in patients with X chromosome abnormalities. Design and method: Observational, prospective study with 7 years of evolution. Inclusion Criteria: Presence of aberrations that affect the number or morphology of the X chromosome in karyotype study. Exclusion Criteria: Those who did not give their informed consent to participate in the study. The detection of Y chromosome sequences was performed. The cardiovascular risk factors present were analyzed. Furthermore, exploration of carotid intimal thickness is by ultrasound was performed. The degree of dynamic endothelial dysfunction in the brachial artery (BMD) was also determined. ACE2 and Angiotensin II genes expression were indirectly evaluated in peripheral blood. Results: The monosomy of the X chromosome was the most frequent. There are 57.4% had overweight or obese, 23% had diabetes, 40% had a new diagnosis of hypertension, and 51% had dyslipidemia. In no case, in the patients evaluated with Turner syndrome, was the presence of the Y chromosome sequence found. One patient was found with a short-arm duplication that includes the SHOX gene, evaluated by MLPA. 89% of the patients presented endothelial dysfunction parameters, and 22% presented carotid plaques in the ultrasound study. In multivariate analysis, patients were separated into tertiles, according to the amount of X chromosomal material in the cytogenetic formula to analyze vascular findings. (Table 1) Conclusions: Central obesity present in childhood and adolescence could contribute to the early diagnosis of the metabolic syndrome so characteristic in these patients. The presence of hypertension could have relationship with renin-angiotensin system alterations. Women with monosomy are the ones who would most suffer an early lack of the protective effect of ACE2 with its vasodilator, antiproliferative and antifibrotic properties, among others. The vascular alterations were an independent factor of the variables studied.

Endothelial Dysfunction and Ischemia-Modified Albumin Levels in Males with Diabetic and Nondiabetic Erectile Dysfunction.

In this study, we aimed to determine endothelial dysfunction and ischemia-modified albumin (IMA) levels in patients diagnosed with erectile dysfunction (ED) and to examine the relationship between these and diabetes disease. 86 male patients (46 patients with diabetes, age: 51.5 ± 9.2 and 40 patients with nondiabetes (control group), age: 54.78 ± 12.2) were included in the study. IMA, a new indicator of tissue ischemia and oxidative stress, was checked. Superoxide dismutase (SOD) activity, another oxidative stress indicator, was examined. Endothelin-1 (ET-1), one of the parameters of endothelial dysfunction, was measured. Additionally, endothelial function was evaluated with flow-mediated vasodilatation (FMD). Student's t-test was used for statistical evaluation. p values less than 0.05 were considered statistically significant. SOD activity was significantly lower in the diabetic group than in the control group, and ET-1 was significantly higher (p < 0.001). IMA was found to be significantly higher in the diabetic group than the control group (p < 0.001). FMD was significantly lower in diabetic group compared to the control group (p < 0.002). According to our findings, the co-occurrence of erectile dysfunction and diabetes demonstrates a complex condition that includes endothelial dysfunction, oxidative stress, and tissue ischemia. When the correlation of indicators, which are markers, was examined, the severity of the co-occurrence of diabetes and erectile dysfunction was again demonstrated.