Index Of Endothelial Function Research Articles

Serum Osteocalcin Level is Negatively Associated with Vascular Reactivity Index by Digital Thermal Monitoring in Kidney Transplant Recipients.

Background and Objectives: Osteocalcin is the most abundant noncollagenous protein in bone matrix, which is considered a marker of bone formation. Previous studies indicate that circulating osteocalcin can be expressed by osteoblasts and even by osteoblast-like cells in vessel walls, and it is often associated with arterial stiffness. Our study aims to examine the potential association between osteocalcin levels and endothelial function among kidney transplant (KT) recipients. Materials and Methods: Fasting blood samples were obtained from 68 KT recipients. To measure the endothelial function and vascular reactivity index (VRI), a digital thermal monitoring test (VENDYS) was used. A commercial enzyme-linked immunosorbent assay kit was also utilized to measure serum total osteocalcin levels. In this study, a VRI of less than 1.0 indicated poor vascular reactivity; a VRI of 1.0–2.0 indicated intermediate vascular reactivity; and a VRI of 2.0 or higher indicated good vascular reactivity. Results: Our findings show that 8 KT recipients (11.8%) had poor vascular reactivity (VRI < 1.0), 26 (38.2%) had intermediate vascular reactivity (1.0 ≤ VRI < 2.0), and 34 (50%) had good vascular reactivity. Increased serum osteocalcin levels (p < 0.001) were found to be associated with poor vascular reactivity. Advanced age (r = −0.361, p = 0.002), serum alkaline phosphate level (r = −0.254, p = 0.037), and log-transformed osteocalcin levels (r = − 0.432, p < 0.001) were identified to be negatively correlated with VRI in KT recipients. Multivariable forward stepwise linear regression analysis revealed that the serum level of osteocalcin (β = −0.391, adjusted R2 change = 0.174; p < 0.001) and advanced age (β = −0.308, adjusted R2 change = 0.084; p = 0.005) were significantly and independently associated with VRI in KT recipients. Conclusions: Higher serum osteocalcin level was associated with lower VRI and poorer endothelial dysfunction among KT recipients.

Intermittent hypoxia enhances shear-mediated dilation of the internal carotid artery in young adults.

Cyclic intermittent hypoxia (IH) increases cerebral blood velocity. This enhanced velocity augments the commensurate shear stimulus and may subsequently increase cerebrovascular endothelial function. This study aimed to examine the effects of cyclic IH on hypercapnia-induced shear-mediated dilation of the internal carotid artery (ICA), a potential index of cerebrovascular endothelial function. Shear-mediated dilation was measured in nine adults (22 ± 4 yr) before as well as after 50 min of cyclic IH [5 cycles, 4 min of normoxia, followed by 6 min of hypoxia (target 80% [Formula: see text]) per cycle] and control normoxia (sham, 50 min of continuous normoxia) on separate days (≥72 h apart). ICA diameter and velocity were measured using Doppler ultrasound during cyclic IH and hypercapnia. Shear-mediated dilation was induced by 3 min of hypercapnia (Δ[Formula: see text]; IH: pre 10.1 ± 1.0 mmHg, post 10.8 ± 1.3 mmHg; sham: pre 10.5 ± 1.5 mmHg, post 10.8 ± 1.5 mmHg) and was calculated as the percent rise in peak relative to baseline diameter. Hypoxia increased ICA blood flow and shear rate (SR) during each cycle [blood flow: 322 ± 90 to 406 ± 74 mL/min, P < 0.01; SR: 179 ± 42 to 207 ± 55/s, P = 0.06, baseline to hypoxia (average of last minute of each cycle)], which was normalized during the succeeding normoxic period (blood flow: 322 ± 90 to 329 ± 68 mL/min, P = 0.54, SR: 179 ± 42 to 176 ± 32/s, P = 0.56). As such, shear-mediated dilation increased following cyclic IH (4.6 ± 1.3% to 6.2 ± 2.2%, P < 0.01), but not control normoxia (4.9 ± 1.4% to 4.9 ± 1.4%, P = 0.92). Our data indicate that increased blood flow and SR during cyclic IH enhance shear-mediated dilation of the ICA in young adults. These results suggest that cyclic IH could be used to optimize cerebral vascular health.NEW & NOTEWORTHY We explored the effects of cyclic intermittent hypoxia (IH) on shear-mediated dilation of the internal carotid artery (ICA), a potential index of cerebral endothelial function, in young adults. Cyclic IH increased blood flow and shear rate in the ICA and, as a result, increased shear-mediated dilation of the ICA. These data suggest that cyclic IH could potentially be applied as a nonpharmacological therapy to optimize cerebral vascular health.

Associations Of Fitness, Physical Activity, And Fatness With A New Index Of Endothelial Function

Current methods for assessing endothelial function, an early marker of cardiovascular disease (CVD), are either invasive or use noninvasive methods that are highly operator dependent or require nonreusable expensive probes, thereby limiting their use for CVD risk prediction. PURPOSE: To assess the relationship of fitness, physical activity (PA), and fatness, each a CVD risk factor, with a novel measure of endothelial function. METHODS: This was a cross-sectional data analysis in adults recruited for a study examining the clinical utility of a new device that measures endothelial vasodilator function using a standard BP cuff. The resulting EnDys score is derived from direct calibrated measurements of brachial arterial compliance throughout the entire transmural pressure curve during a staged cuff release after 5 minutes of upper arm occlusion. A higher score means better endothelial function. Fitness was assessed by a 6-minute walk test (6MWT). Self-report of PA was assessed by the Rapid Assessment of Physical Activity tool. Body mass index (BMI) was used as a marker of general fatness and waist circumference (WC) as a marker of abdominal fatness. RESULTS: In all 153 subjects, 51% were female, 7% were smokers, 7% had CVD, and 10% had type 2 diabetes. The mean ± SD for age was 49.3 ± 17.2, EnDys was 80.8 ± 30.4, BMI was 29.3 ± 6.9 kg/m2, WC was 37.5 ± 6.7 inches, and 6MWT was 495.4 ± 113.5 meters. EnDys was higher in females, 87.6 ± 30.5, vs males, 73.8 ± 28.9, p<0.01. EnDys did not differ by being sedentary, 80.8 ± 27.6, or active, 81.0 ± 33.0, p=0.97. Using bivariate analysis, a lower EnDys was associated with higher BMI, r=-0.23, higher WC, r=-0.33, lower 6MWT, r=0.32, and older age, r=-0.20, all p<0.02 or less. In a multivariate model, 6MWT (β=-0.06, p<0.01), WC (β=-1.02, p<.02), and sex (female, β=6.9, p<0.01) were each independently associated with EnDys. There were no interactions for sex with 6MWT and WC. CONCLUSION: Among measures of fitness, PA, and fatness, and in both sexes, a lower walking distance and a higher waist circumference were each independently associated with a lower EnDys, indicating worse endothelial function. A next logical step is to assess if EnDys improves with interventions like exercise and weight loss, thereby providing a novel and relatively simple way to track progress towards CVD risk reduction.

Acute Hypotension Blunts Brachial Flow-mediated Dilation In Young Healthy Men

Recent clinical studies using a vasovagal syncope suggest that endothelial function is a key factor controlling blood pressure (BP) regulation during acute hypotension. Acute increase in BP is known to attenuate brachial flow-mediated dilation (FMD). However, the influence of acute hypotension on peripheral FMD remains unclear. PURPOSE: To test the hypothesis that acute hypotension blunts brachial FMD, an index of endothelial function, in young healthy humans. METHODS: Twelve healthy men (21.8±1.6 yrs; body mass index: 22.2±1.6 kg/m2, mean±standard deviation) underwent 3 trials of brachial FMD measurement. The trials involved a standardized FMD protocol (control trial), a trial with an abrupt decrease in BP via both thigh-cuff inflation and the deflation method (hypotension trial), and a trial with a decrease in shear rate (SR) via a shortened occlusion time for 3 min without a change in BP (SR reduction trial). Trials were randomized with 30-min intervals during a single visit. Duplex ultrasound was employed to measure brachial diameter and blood velocity. BP and heart rate were continuously measured using a non-invasive beat-to-beat BP monitoring system. To adjust the effect of SR area under the curve (SRAUC) on FMD, normalized FMD were calculated. RESULTS: There was a marked fall in mean arterial pressure during reactive hyperemia in the hypotension trial (−24±6 mmHg), but not in the control and SR reduction trials. SRAUC was attenuated in the SR reduction trial (p<0.001), but not in the hypotension trial (p=0.316), compared with the control trial. Thus, FMD was attenuated in the hypotension and SR reduction trials compared with the control trial (p=0.003 and p=0.043, respectively). The attenuation in FMD was greater in the hypotension trial than in the SR reduction trial (p=0.006; control, 6.9%±3.5%; hypotension, 3.5%±1.7%; SR reduction, 5.0%±2.2%). After adjusting FMD using SRAUC, the normalized FMD remained attenuated in the hypotension trial (p=0.014), but not in the SR reduction trial (p>0.05). CONCLUSION: Current findings indicate that BP could be an important determinant of FMD. Blunted FMD of the peripheral arteries may be a physiological response to restore BP and/or prevent a further reduction in BP following acute hypotension in healthy humans.

64effects of long-term exercise training and detraining on endothelial function and arterial stiffness in patients with atrial fibrillation: a randomized controlled trial with 1-year follow-up

Abstract Introduction Exercise training (ET) improves endothelial function and arterial stiffness in patients with cardiovascular disease. However, whether ET improves endothelial function and arterial stiffness in patients with atrial fibrillation (AF) is unclear. If it does, for how long the effects are sustained remains to be determined. Methods In a prospective study, 58 patients with AF (age, 62 ± 7 years) were randomized into an ET group for 12 months (CT, n = 13), a group with 6-month detraining after a 6-month ET (DT, n = 15), and a medical treatment only group (MT, n = 30). For ET, cycling on a bicycle ergometer was performed in the DT and CT groups 3 times a week for 6 and 12 months, respectively. Each session started with a 10-minute warmup at 60% to 70% of the maximal heart rate (HRpeak), followed by four 4-minute intervals at 80% to 90% of the HRpeak, with 3 minutes of active recovery at 60% to 70% of the HRpeak between intervals, ending with a 5-minute cooldown period. Peak exercise oxygen consumption (Vo2), intimal-medial thickness (IMT) of the carotid artery measured on high-resolution ultrasonography, and left ventricular function were measured at baseline, after 6 months of training, and after additional 6 months of continuous training or detraining follow-up assessments. In addition, plasma von Willebrand factor (vWF), endothelin-1, nitric oxide, tumour necrosis factor alpha, interleukin-1 beta, interleukin-6, and interleukin-10 levels were measured as indices of endothelial function. Results The 6-month ET increased peak Vo2 (CT: 29.0 ± 6.5 ml/[kg·min] and DT: 26.0 ± 8.2 ml/[kg·min] vs. MT: 23.0 ± 5.2 ml/[kg·min], p = 0.04) and decreased plasma vWF levels (CT: 103.7 ± 30.7 IU/dL and DT: 106.0 ± 31.2 IU/dL vs. MT: 145.0 ± 47.7 IU/dL, p = 0.01). Detraining significantly reduced the ET-induced increase in Vo2 and decreased the vWF to baseline level, although continuous ET maintained changes in Vo2 (CT: 28.1 ± 5.3 ml/[kg·min] and DT: 22.4 ± 6.6 ml/[kg·min] vs. MT: 21.5 ± 4.8 ml/[kg·min], p = 0.043) and in vWF (CT: 84.3 ± 39.1 IU/dL vs. DT: 122.2 ± 27.5 IU/dL and MT: 135.9 ± 50.4 IU/dL, p = 0.014). However, carotid arterial IMT, and resting left ventricular systolic and diastolic functions showed no significant changes, with no inter-group differences after 6 months of training and 6 months of continuous training or detraining. Conclusions The decreased vWF level suggested that ET can be a strong non-pharmacologic option to improve endothelial function in patients with AF. However, it can rapidly lose its effects after detraining. Therefore, physicians should encourage their patients to participate in a continuous exercise program to sustain its benefits in terms of improved exercise capacity and endothelial function in patients with AF.

The relationship between pulse waveform analysis indices, endothelial function and clinical outcomes in patients with peripheral artery disease treated using percutaneous transluminal angioplasty during a one-year follow-up period

Several predictors of clinical outcomes after percutaneous transluminal angioplasty (PTA) interventions in patients with peripheral arterial disease (PAD) have been investigated. Indices of endothelial function, arterial pulse waveform analysis (aPWA) and markers of peripheral artery ischemia were among the most commonly examined. The aim of the current study was to assess the relationship between potential predictors of clinical outcomes after peripheral artery PTA during a 1-year follow-up period. The study included 72 individuals with PAD at a mean age of 66.3 ± 7.2 (79.1% males). All patients underwent PTA of the peripheral arteries. Among them, 42.8% presented critical limb ischemia (CLI). During the first visit and at 1 month and 6 months after PTA, endothelial function and aPWA measurements were taken. Ankle-brachial index (ABI), toe-brachial index (TBI) and physical evalu-ation of the limbs took place during the first visit and at 1, 6 and 12 months after the PTA. The study endpoints included myocardial infarction, amputation, death, stroke and reintervention. All subjects included in the study were observed for 386 days after the PTA. A significant improvement was noted in walking distance after PTA at the following time points, as well as transient improvement of ABI and flow-mediated dilatation (FMD) and no significant change in aPWA indices and reactive-hyperaemia index (RHI). The mean ABI, TBI, FMD and RHI values did not correlate with each other at baseline. There were 25 study endpoints which occurred in 16 patients during the follow-up period (22.2%). Patients with CLI, hypercholesterolemia, lower dias-tolic blood pressure, higher subendocardial viability ratio, a greater number of pack-years and lower TBI at baseline presented significantly poorer clinical outcomes in terms of endpoint events. Endothelial function assessed as FMD and reactive hyperemia-peripheral arterial tonometry (RH-PAT) before PTA in patients with advanced PAD do not predict clinical outcomes during the 1-year follow-up.

Vasculotoxicity of Chemotherapy: Assessment оf Endothelial Dysfunction Biomarkers' Levels in Gastric Cancer Patients

Aim To evaluate dynamics of biomarkers for endothelial dysfunction (ED), including endothelin-1 (ET-1) and von Willebrand factor (VWF) in patients with stomach cancer (adenocarcinoma) before and after polychemotherapy (PCT); to compare these results with respective values in healthy volunteers and patients with cardiovascular diseases (CVD); to study correlations of the ED biomarkers with indexes of instrumental evaluation of endothelial dysfunction.Material and methods The study included 75 participants, including 25 healthy volunteers (control group), 25 patients with documented CVDs (arterial hypertension + ischemic heart disease), and 25 patients of the main group with histologically documented stage II-IV stomach cancer (adenocarcinoma) who received different courses of PCT with platinum-based agents (oxaliplatin, cisplatin) and fluoropyrimidines (5 fluorouracil, capecitabin). Laboratory measurement of ED biomarkers, computerized nailfold video capillaroscopy (CNVC), and finger laser photoplethysmography (PPG) (methods for noninvasive evaluation of vascular wall and ED), electrocardiography, 24-h ECG Holter monitoring, and echocardiography (EchoCG) were performed for all patients of the main group prior to PCT and within one months after the last course completion. This evaluation was performed once for healthy volunteers and patients of the CVD group upon inclusion into the study.Results In the main group, ET-1 levels were non-significantly lower than normal and did not change during the courses of antitumor treatment (0.95 [0.6; 1.4] and 0.94 [0.7; 1.4] pg /ml (р&lt;0.9) before and after PCT, respectively). Statistically significant differences were found between the control group and oncological patients after the treatment (р&lt;0.04). Levels of VWF remained within the normal range in all examined participants and did not significantly differ between study groups, including oncological patients before and after the specific treatment (р&gt;0.05 for all comparisons). The correlation analysis detected significant correlations of ET-1 levels with functional disorders of microcirculation, ET-1 with the occlusion index (rs=0.56; p=0.005), ЕТ-1 with percentage of capillary restoration (PCR, rs= -0.72; p=0.018) and with the incidence rate of supraventricular extrasystole (rs=0.48; p=0.032).Conclusion The dynamics of ED biomarkers was studied for the first time in patients with stomach cancer receiving a specific antitumor therapy. Although no significant changes in ЕТ-1 and VWF were observed during the PCT (probably due to exhaustion of the endothelial system and a small patient sample), these indexes can be considered as early vasculotoxicity markers due to the presence of significant correlations with indexes of impaired endothelial function according to the results of instrumental evaluation.

Oxidative Stress and Endothelial Dysfunction in the Development of Simulated Radio-Induced Lung Damage and their Correction with Pulmonary Surfactant

Radiation exposure to the chest organs used in the complex treatment of neoplasms is often accompanied by the development of radiation pneumonitis, fibrosis and respiratory failure.The aim of the study was to evaluate oxidative stress and endothelial dysfunction in radio-induced lung damage and possibility of their correction with a pulmonary surfactant preparation.Material and methods. Lung tissue samples of 82 male Wistar rats were investigated in the study. Single local irradiation of animals was performed with the X-ray RUM-17 unit at a dose 12 Gy. The quantitative content and fractional composition of phospholipids of pulmonary surfactant were determined in the study. Oxidative stress was detected using Raman spectroscopy, endothelial dysfunction was detected immunohistochemically.Results. Oxidative stress and endothelial dysfunction were registered starting from the first day of the experiment, and manifested by an increased content of free radicals and a decrease in endothelial function indices supported by precise spectroscopic, immunohistochemical and electron microscopic methods. With application of Surfactant-BL preparation oxidative stress manifestations were eliminated to the beginning of the intermediate stage of the experiment, and were preserved without correction until its completion.Conclusions. Three-fold intratracheal administration of a pulmonary surfactant preparation implements an antioxidant, immunomodulatory and compensating effect attenuating the alterative effect of oxidative stress and its initiating impact on the development of endothelial dysfunction. Native surfactant having a pronounced effect on all components of the lung tissue including alveolocytes of the first and second types and endothelial cells of the capillaries of the lung results in the correction of endothelial dysfunction.

SUN-168 Low Serum Adiponectin Levels are Associated with Endothelial Dysfunction in Non-Dialysis Dependent Chronic Kidney Disease Patients

Cardiovascular disease, which mainly contributed from atherosclerosis, is the leading cause of death in patients with chronic kidney disease (CKD). Beyond the well-known traditional risk factors, endothelial dysfunction is closely associated with cardiovascular mortality and is highly prevalent in patients with CKD. Moreover, adipose tissue, which secreted various adipokines, was shown to play a critical role in the regulation of endothelial function. We aimed to evaluate the correlation of endothelial function with serum levels of adiponectin and leptin in patients with non-dialysis CKD. A total of 130 non-dialysis CKD patients, aged 65.4 ± 11.9 years, were recruited. Serum adiponectin levels were measured using a commercially available enzyme immunoassay kit. Endothelial function and vascular reactivity index (VRI) were measured using digital thermal monitoring test. In this study, VRI < 1.0, VRI 1.0–1.9, and VRI ≥ 2.0 were defined as poor, intermediate, and good vascular reactivity, respectively. Among them, 22 (16.9%) patients had poor VRI, who exhibited an elevated serum BUN (P = 0.037), decreased eGFR (P = 0.047) and serum adiponectin levels (P < 0.001). After multivariate adjustment in linear regression, serum BUN levels (β = -0.176, adjusted R2 change = 0.025; P = 0.021) and adiponectin levels (β = 0.487, adjusted R2 change = 0.256; P < 0.001) were independently associated with VRI values in non-dialysis CKD patients. Serum fasting adiponectin levels were positively associated with VRI values among non-dialysis CKD patients. Further studies are required to elucidate the relationship between endothelial function and adiponectin levels in non-dialysis CKD patients.

Triamcinolone acetonide combined with aminoguanidine inhibits inflammation and oxidative stress, improves vascular endothelial and retinal function and reduces VEGF expression in diabetic retinopathy patients.

Effects of triamcinolone acetonide (TA) combined with aminoguanidine (AG) on vascular endothelial function, vascular endothelial growth factor (VEGF) expression and retinal function in diabetic retinopathy (DR) patients were studied. A total of 100 patients with DR admitted to the Taizhou Second People's Hospital Affiliated to Yangzhou University from January 2016 to December 2018 were collected and randomly divided into observation group (n=50) and control group (n=50). The control group was only treated with TA (4 mg), while the observation group was additionally treated with AG (50 mg/kg). The therapeutic effect and adverse reactions were observed, and the changes in blood glucose (GLU), blood lipid, serum inflammatory cytokines and oxidative stress indexes before and after treatment were detected. Moreover, the serum VEGF level was examined, the central macular thickness (CMT), retinal neovascularization (RNV) leakage area and best corrected visual acuity (BCVA) of retinopathy were observed, and the vascular endothelial function indexes such as nitric oxide (NO), endothelin-1 (ET-1) and intercellular adhesion molecule-1 (ICAM-1) were detected. The therapeutic effect in the observation group was significantly better than that in control group (P<0.05). In observation group after treatment, the levels of GLU, total cholesterol (TC), triglyceride (TG), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO), malondialdehyde (MDA) and catalase (CAT) in the serum, VEGF, CMT and RNV, as well as NO, ET-1 and ICAM-1 were remarkably decreased (P<0.05), while those of superoxide dismutase (SOD) and BCVA were evidently increased (P<0.05). The changes were more significant at 3 months after treatment than those at 1 month. TA combined with AG can inhibit inflammation and oxidative stress, improve vascular endothelial function and retinal function and reduce VEGF expression in DR patients. The overall effect of the combined therapy is good, and its application is worth popularizing.

Atherosclerosis, inflammatory factor changes, cognitive disorder and vascular endothelial functions in patients with different grades of leukoaraiosis.

To study the atherosclerosis (AS), inflammatory factor level, cognitive disorder and vascular endothelial functions in patients with different grades of leukoaraiosis (LA), and to explore the correlations of different grades of LA with cognitive disorder. A total of 180 patients with cerebral infarction admitted and treated in the Department of Neurology of our hospital were selected, and they were graded according to the Tarvonen-shcolder standard, with 45 patients in each group. The atherosclerotic plaques of the patients were detected via a color Doppler ultrasound system and magnetic resonance imaging (MRI). Their inflammatory factor levels were determined using enzyme-linked immunosorbent assay (ELISA). The cognitive function was scored based on the mini-mental state examination (MMSE), and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), endothelin (ET) and nitric oxide (NO) were measured to evaluate vascular endothelial functions. According to the comparisons among four groups of the patients, the incidence rate of AS was gradually increased among patients with different grades of LA (p < 0.05). With the aggravation of LA, the levels of inflammatory factors in patients were obviously increased (p < 0.05). LA patients had evidently lowered MMSE scores and levels of SOD and NO, but notably raised inflammatory factors C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9) and vascular endothelial function indices MDA and ET (p < 0.05). The occurrence of LA is implicated with the increasing levels of inflammatory factors in the patients, aggregation of cognitive dysfunction and impairment vascular endothelial functions.

Diagnostic Criteria of Flow‐Mediated Vasodilation for Normal Endothelial Function and Nitroglycerin‐Induced Vasodilation for Normal Vascular Smooth Muscle Function of the Brachial Artery

BackgroundDiagnostic criteria of flow‐mediated vasodilation (FMD), an index of endothelial function, and nitroglycerin‐induced vasodilation (NID), an index of vascular smooth muscle function, of the brachial artery have not been established. The purpose of this study was to propose diagnostic criteria of FMD and NID for normal endothelial function and normal vascular smooth muscle function.Methods and ResultsWe investigated the cutoff values of FMD and NID in subjects with (risk group) and those without cardiovascular risk factors or cardiovascular diseases (no‐risk group) in 7277 Japanese subjects (mean age 51.4±10.8 years) from the Flow‐Mediated Dilation Japan study and the Flow‐Mediated Dilatation Japan Registry study for analysis of the cutoff value of FMD and in 1764 Japanese subjects (62.2±16.1 years) from the registry of Hiroshima University Hospital for analysis of the cutoff value of NID. Receiver‐operator characteristic curve analysis of FMD to discriminate subjects in the no‐risk group from patients in the risk group showed that the optimal cutoff value of FMD to diagnose subjects in the no‐risk group was 7.1%. Receiver‐operator characteristic curve analysis of NID to discriminate subjects in the no‐risk group from patients in the risk group showed that the optimal cutoff value of NID to diagnose subjects in the no‐risk group was 15.6%.ConclusionsWe propose that the cutoff value for normal endothelial function assessed by FMD of the brachial artery is 7.1% and that the cutoff value for normal vascular smooth muscle function assessed by NID of the brachial artery is 15.6% in Japanese subjects.Clinical Trial Registration http://www.umin.ac.jp Unique identifiers: UMIN000012950, UMIN000012951, UMIN000012952, and UMIN000003409

Relationship of serum inflammatory cytokines with anemia and vascular endothelial function in children with systemic lupus erythematosus.

To analyze the relationship of the serum levels of inflammatory cytokines with the degree of anemia and vascular endothelial function in children with systemic lupus erythematosus (SLE), as well as to explore the predictive value of risk factors for SLE in children. A total of 88 patients with SLE diagnosed in the Pediatric Department of our hospital from March 2015 to February 2017 were selected as the observation group, and 30 healthy controls with comparable age were selected as the control group. Basic characteristics of all enrolled individuals, such as age, sex, height and weight, and the related biochemical indexes, including the levels of inflammatory cytokines [C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR)], blood routine test including hemoglobin (Hb), platelet (PLT) and mean corpuscular volume as well as related indexes of vascular endothelial function, such as homocysteine (Hcy), carbonic oxide (NO), endothelial nitric oxide synthase (eNOS) were measured. In addition, the SLE disease activity index (SLEDAI) score of patients was also recorded. There were no significant differences regarding age, sex, body mass index (BMI), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) between observation group and control group (p > 0.05), but the total cholesterol (TC) level in observation group was significantly higher than that in control group (p < 0.05). In addition, the levels of CRP, TNF-α, IL-6 and ESR in serum in observation group were significantly higher than those in control group (p < 0.05). However, the Hb, PLT and mean corpuscular volume in observation group were significantly lower than those in control group (p < 0.05). Moreover, the levels of Hcy, NO and eNOS in observation group were significantly higher than those in control group (p < 0.05). Furthermore, correlation analyses showed that CRP was positively correlated with SLEDAI score (r = 0.791, p < 0.001) and Hcy level (r = 0.817, p < 0.001), but negatively correlated with Hb level (r = -0.663, p < 0.001). There is a close relationship between serum inflammatory cytokines and SLE severity, Hcy or Hb level in children, suggesting these inflammatory cytokines might be novel indicators for evaluating the severity of SLE.

The Effect of Perimenopausal Transdermal Estradiol and Micronized Progesterone on Markers of Risk for Arterial Disease.

The arterial effects of hormone therapy remain controversial. This study tested the effects of transdermal estradiol plus intermittent micronized progesterone (TE + IMP) in healthy perimenopausal and early postmenopausal women on several mechanisms involved in the pathophysiology of arterial disease. Healthy perimenopausal and early postmenopausal women, ages 45 to 60 years, were enrolled in this randomized, double-blind, placebo-controlled trial. Women were randomized to receive TE (0.1 mg/day) + IMP (200 mg/day for 12 days) or identical placebo patches and pills for 12 months. Outcomes included: change in stress reactivity composite z-score (combining inflammatory, cortisol, and hemodynamic responses to a standardized psychological laboratory stressor); flow-mediated dilation (FMD) of the brachial artery (an index of vascular endothelial function); baroreflex sensitivity; and metabolic risk (presence of the metabolic syndrome or insulin resistance), all assessed at baseline and at months 6 and 12. Of 172 women enrolled, those assigned to TE + IMP tended to have higher resting baroreflex sensitivity than those assigned to placebo across the 6- and 12-month visits. Although treatment groups did not differ in terms of the other prespecified outcomes, a significant treatment-by-age interaction was found for FMD and stress reactivity such that an age-related decrease in FMD and increase in stress reactivity were seen among women assigned to placebo but not those assigned to TE + IMP. Women on TE + IMP also had lower resting diastolic blood pressure, lower levels of low-density lipoprotein cholesterol, and higher baroreflex sensitivity during stress testing. TE + IMP tended to improve cardiac autonomic control and prevented age-related changes in stress reactivity and endothelial function among healthy perimenopausal and early postmenopausal women.

Endothelial function and arterial stiffness indices remain unchanged following intensification of glycemic control in poorly controlled patients with long-standing type 2 diabetes mellitus

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Acute hypotension attenuates brachial flow-mediated dilation in young healthy men.

This study aimed to test our hypothesis that acute hypotension attenuates brachial flow-mediated dilation (FMD) as an index of endothelial function in healthy humans. Twelve healthy men (21.8 ± 1.6years, body mass index; 22.2 ± 1.6kg/m2) participated in this study. Brachial FMD was measured in three trials: standardized FMD protocol (control trial), abrupt decrease in blood pressure (BP) via thigh cuff inflation-deflation (hypotension trial) and decrease in shear rate (SR) via a shortened forearm occlusion time (SR reduction trial). Brachial diameter and blood velocity were measured using Duplex ultrasound. Mean arterial pressure during reactive hyperaemia showed a marked decrease in the hypotension trial (- 23.7 ± 6.0mmHg), but not in the control and SR reduction trials. SR area under the curve was attenuated in the SR reduction trial (P < 0.001), but not in the control and hypotension trials (P = 0.316). Consequently, FMD was attenuated in the hypotension and SR reduction trials compared with that in the control trial (P = 0.003 and P = 0.043, respectively), and was attenuated to a greater extent in the hypotension trial compared with the SR reduction trial (P = 0.006; control, 6.9 ± 3.5%; hypotension, 3.5 ± 1.7%; SR reduction, 5.0 ± 2.2%). After adjusting FMD using SR, FMD remained attenuated in the hypotension trial (P = 0.014), but not in the SR reduction trial. Our findings indicate that arterial pressure as well as sympathetic nervous system activation could be an important determinant of FMD. Blunted FMD of peripheral arteries may be a rational response to restore BP and/or prevent further reduction of BP following acute hypotension in healthy humans.

Prognosing a severe course of asthma in children following the study of endothelial function

Abstract Background Asthma is a common disease with increasing prevalence in children and adults. The WHO estimates that annually 15 million disability-adjusted life-years are lost, and 250,000 asthma deaths are reported worldwide. Approximately, 500,000 annual hospitalizations are due to asthma (1). Aim In our study, we aimed to evaluate the endothelial function in children with asthma in remission and the prognosis of severe asthma. Materials and methods The study involved examination of 91 children, aged 6–17 years, with persistent asthma in the remission period. Indices of endothelial function (soluble vascular molecule of intercellular adhesion-1 [sVCAM-1], concentration of stable metabolites of nitric oxide in blood serum [NO2 +NO3 ], thickness of the intima-media complex [IMC] of the common carotid artery (CCA), and endothelium-dependent dilatation of the brachial artery [FMD%]). Statistical analyses were performed with StatSoft STATISTICA Version 8 (Tulsa, OK). To determine the relation between qualitative characteristics, the criterion χ2 was used, and the procedure of multiple logistic regression analysis was performed. Results The endothelium parameter levels (FMD% [H = 46.02], IMC [H = 60.75], NO2 + NO3 [H = 40.82], and sVCAM-1 [H = 76.57, p = 0.0000]) depend on the severity of the disease. The study showed that the factors that should be taken into account in prognosis of the formation of the severe course of asthma include positive family allergic history, serum sVCAM-1 and NO2 + NO3 levels, and the thickness of IMC CCA. Conclusions All the children with asthma in the remission period were found to have endothelial dysfunction. The degree of disruption of the function of the endothelium depends on the severity of the course of asthma. An algorithm for predicting the severe course of asthma in children has been developed.

Subclinical inflammation and endothelial dysfunction are linked to cardiac autonomic neuropathy in type 2 diabetes.

The present study aimed to examine association between inflammatory and endothelial function biomarkers and indices of cardiac autonomic control in T2DM patients. 50 T2DM patients were recruited for this study. For cardiac autonomic function, cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV) analysis was performed. Blood samples were collected for evaluating inflammatory and endothelial function biomarkers. Multivariable linear regression analysis adjusted for diabetes duration, glycemic control, waist circumference, hypertension, dyslipidemia, metformin, and statins was performed to examine the association between the biomarkers and cardiac autonomic function parameters. Interleukin-6 was inversely related to total power (p= .009) and low frequency power (p= .04). Interleukin-18 and high sensitivity C-reactive protein inversely correlated with measures of cardiac vagal control (p < .05). Both nitric oxide and endothelial nitric oxide synthase were positively linked with cardiac vagal control indices (p < .05) whereas endothelin-1 did not show any independent association with cardiac autonomic function parameters. Biomarkers of inflammation and endothelial function are associated with measures of cardiac vagal control and global HRV which suggest that there is some pathophysiological link between subclinical inflammation, endothelial dysfunction and cardiac autonomic dysfunction in T2DM.

Common bean protein hydrolysate modulates lipid metabolism and prevents endothelial dysfunction in BALB/c mice fed an atherogenic diet

Background and aimsCommon beans (Phaseolus vulgaris L.) protein hydrolysate is a source of bioactive peptides with known health benefits. The aim of this study was to evaluate the effect of common bean protein hydrolysate on lipid metabolism and endothelial function in male adult BALB/c mice fed an atherogenic diet for nine weeks. Methods and resultsMale adult mice were divided into three experimental groups (n = 12) and fed with normal control diet; atherogenic diet and atherogenic diet added with bean protein hydrolysate (700 mg/kg/day) for nine weeks. Food intake, weight gain, lipid profile, Atherogenic Index of Plasma, inflammation biomarkers and endothelial function were evaluated. APH group presented reduced feed intake, weight gain, lipid profile, tumor necrosis factor-α, angiotensin II (94% and 79%, respectively) and increased endothelial nitric oxide synthase (62%). ConclusionsProtein hydrolysate showed hypocholesterolemic activity preventing inflammation and dysfunction of vascular endothelium, in addition to decreasing oxidative stress, indicating an adjuvant effect on reducing atherogenic risk.

Serum Adipocyte Fatty Acid-Binding Protein Level is Negatively Associated with Vascular Reactivity Index Measured by Digital Thermal Monitoring in Kidney Transplant Patients.

Adipocyte fatty acid-binding protein (A-FABP) is abundantly found in mature adipocytes and is involved in cardiovascular disease. Our aim is to investigate the association between serum A-FABP levels and endothelial function among kidney transplant (KT) patients. Fasting blood samples were obtained from 80 KT patients. Serum A-FABP levels were measured using a commercially available enzyme immunoassay kit. Endothelial function and vascular reactivity index (VRI) were measured using digital thermal monitoring test. In this study, VRI < 1.0, VRI 1.0–1.9, and VRI ≥ 2.0 were defined as poor, intermediate, and good vascular reactivity, respectively. There were 12 (15.0%), 30 (37.5%), and 38 (47.5%) KT patients categorized as having poor, intermediate, and good vascular reactivity, respectively. Increased serum levels of alkaline phosphatase (p = 0.012), γ-glutamyltranspeptidase (GGT; p = 0.032), and A-FABP (p < 0.001) were associated with decreased vascular reactivity. Multivariable forward stepwise linear regression analysis revealed that age (β = −0.283, adjusted R2 change = 0.072; p = 0.003) and serum log-A-FABP level (β = −0.514, adjusted R2 change = 0.268; p < 0.001) were significantly associated with VRI values in KT patients. We concluded that serum fasting A-FABP level is negatively associated with VRI values and plays a role in endothelial dysfunction of KT patients.