Markers Of Endothelial Function Research Articles

The Effects Of Acute Consumption Of A Brewed Cocoa Beverage On Endothelial Function

Previous studies have shown that the polyphenol components of cocoa can improve the health and function of blood vessels. It is currently unknown whether consuming a brewed drink made from roasted cocoa beans has the same beneficial effects on blood vessel function. PURPOSE: The purpose of this study was to assess the acute effects of consuming brewed cocoa on resting blood pressure and endothelial function using near-infrared spectroscopy (NIRS) to evaluate changes in tissue oxygen saturation (StO2) following blood vessel occlusion. METHODS: A total of 15 healthy college-aged adults participated in this study. StO2 levels were monitored continuously throughout the test using a NIRS device placed on the flexor digitorum profundus of the dominant arm. Baseline StO2 levels were measured for 5 minutes following 10 minutes of supine rest, after which blood flow to the forearm was occluded for 3 minutes using a blood pressure cuff inflated to 50mmHg above resting systolic pressure, followed by a 5-minute period of reperfusion following release of the cuff. Subjects then consumed either plain water, or the cocoa treatment (40g of roasted cocoa brewed for 10 minutes), and all testing was repeated 90 minutes later. Subjects returned to the lab on a separate day to repeat the test using the opposite beverage. RESULTS: The change from baseline was not significantly different between water (W) and cocoa (C) for resting heart rate (C= -6.6+6.5 bpm, W= -4.4+7.0 bpm; p=0.29), resting systolic blood pressure (C= 0.9+4.5 mmHg, W= -2.2+7.4 mmHg; p=0.10), resting diastolic blood pressure (C= -1.1+6.7 mmHg, W= 0.8+4.5 mmHg; p=0.39), pre-occlusion StO2 (C= 1.6+5.6 %, W= -1.9+6.9%; p=0.06), minimum StO2 during occlusion (C= -0.6+10.5 %, W= -0.7+12.8%; p=0.98), reperfusion maximum StO2 (C= 0.5+3.6 %, W= -0.8+5.0 %; p=0.40), or reperfusion rate quantified as the slope of the StO2 during the first 10 seconds of reperfusion (C= 0.1+0.4 % s-1, W= 0.06+0.4 % s-1; p=0.79). CONCLUSION: Consumption of a brewed cocoa drink does not significantly affect markers of endothelial function or blood pressure in healthy college-aged adults.

Improvement of microcirculatory impairment in patients with predialysis chronic kidney disease after AST-120 administration

BackgroundEndothelial dysfunction starts at an earlier stage in patients with chronic kidney disease (CKD), and induces macro- and microcirculatory impairments. We evaluated whether uremic toxin-lowering therapy could improve endothelial function in patients with CKD.MethodsWe performed a prospective interventional trial with 30 predialysis non-diabetic CKD patients who were administered oral adsorbent AST-120 (6 g/day) for 12 months. Surrogate markers of endothelial function including flow-mediated dilation (FMD) and skin perfusion pressure (SPP) were serially evaluated along with serum indoxyl sulfate (IS) levels and renal function. Renal function was evaluated based on blood urea nitrogen, serum creatinine (sCr) levels, and estimated glomerular filtration ratio (eGFR).ResultsMonthly decline in renal function (slope of reciprocal sCr) after AST-120 administration did not change compared to that during the pre-treatment period. However, serum IS levels significantly decreased at 3 months after AST-120 administration (p < 0.01), and it was sustained during the period of AST-120 administration (p < 0.01). Although FMD did not improve, SPP was constantly elevated after AST-120 administration, and was significantly higher at 12 months compared with baseline value (69.7 ± 14.6 vs. 78.8 ± 18.9 mmHg, p < 0.05). A significant correlation between the change of IS and SPP from baseline values was shown at 6 months after AST-120 administration (r = − 0.558, p = 0.02).ConclusionMicrocirculatory impairment was improved after AST-120 administration in patients with predialysis CKD.Trial registrationUMIN, UMIN000013577. Registered on March 31, 2014,

Sprint and endurance training in relation to redox balance, inflammatory status and biomarkers of aging in master athletes

PurposeStudies have shown a positive influence of intense athletic training on several biomarkers of aging, but it remains unclear whether this influence is dependent of exercise-training-mode. This study compared redox balance, cytokine levels and biomarkers of aging between master sprinters and endurance athletes, as well as in young and middle-aged individuals as controls. MethodsParticipants were male master sprinters (SA, 50 ± 8.9yrs; n = 13) and endurance runners (EA, 53 ± 8.2yrs; n = 18) with remarkable athletic experience (~25yrs of practice), besides untrained young (YC, 22.7 ± 3.9yrs; n = 17) and age-matched controls (MC, 45.5 ± 9.8yrs; n = 12). Anamnesis, anthropometrics, biomarkers of aging, inflammation status and oxidative stress parameters were analyzed in all participants. ResultsAn increased pro-oxidant activity (elevated protein carbonyl; isoprostanes and 8-OHdG) was observed for MC in comparison to remaining groups (p < 0.05). However, SA presented a better antioxidant capacity than both MC and EA, while nitrite/nitrate (NOx) availability was higher for EA and lower for the MC (p < 0.05). Both groups of athletes presented a better anti-inflammatory status than MC (increased IL-10 and lowered IL-6, sIL-6R, sTNF-RI), but worse than YC (increased TNF-α, sTNF-RI, and sIL-6R) (p < 0.05). Telomere length was shorter in MC, which also had lower levels of irisin and klotho, and elevated FGF-23 (p < 0.05). ADMA levels were higher in MC and SA, while irisin was lower in EA when compared to SA and YC (p < 0.05). ConclusionMaster athletes presented better redox balance and inflammatory status, with decreased biomarkers of aging compared to control. Regarding exercise mode, a better NO- profile, as a marker of endothelial function, was observed for EA, whereas SA had a better redox balance, cytokines profile and attenuated biomarkers of aging.

The dynamics of endothelial dysfunction markers among patients with pulmonary hypertension on the background of chronic obstructive pulmonary disease under the influence of treatment

The objective of the research - to determine the dynamics of endothelial dysfunction markers among patients with pulmonary hypertension on the background of chronic obstructive pulmonary disease under the influence of treatment.Material and methods. The results of the study are based on data from a comprehensive survey of 170 patients with chronic obstructive pulmonary disease (COPD) aged from 40 to 65 years, 123 of which had pulmonary hypertension and 47 ones had no pulmonary hypertension. Also 31 almost healthy people were examined on an outpatient basis. Patients with pulmonary hypertension on a background of COPD were divided into two subgroups of observations depending on the treatment. The first subgroup was used as the background therapy and the second subgroup - background therapy with the roflumilast. Markers of endothelial function were determined during screening and after 12 months of follow-up.Results. The median level of endothelin-1 in the group of patients with pulmonary hypertension on the background of COPD was 3.17 [2.19 ; 4.14] fmol/ ml and was significantly higher, both against the value of 1.78 [1.25 ; 2.18] fmol/ml in the group of COPD patients without pulmonary hypertension (p &lt; 0.05), and 10.2 times higher than versus the level of 0.31 [0.19 ; 0.36] fmol/ml in the group of healthy individuals (p&lt;0.05). The amount of nitrogen oxide metabolites (NO2+NO3) was significantly lower (by 15.8 %) in the group of patients with pulmonary hypertension on the background of COPD versus the value of 22.00 [21.00 ; 23,00] mmol/l in the group of COPD patients without pulmonary hypertension, and is 37 % lower than in the group of healthy individuals, where the level of this indicator was 26,00 [25,00 ; 28,00] mmol/l (p&lt;0.05). Then a correlation analysis was performed. Significant relationships were determined between the following indicators: duration of COPD and NO3 level (R = -0.29, p = 0.001); duration of COPD and NO2+ NO3 level (R - 0.26, p = 0.003); mean pulmonary artery pressure and endothelial-1 level (R = +0.70, p = 0.001); mean pulmonary artery pressure and NO2 level (R = -0.59, p = 0.001); mean pulmonary artery pressure and NO2+ NO3 (R = -0.50, p = 0.001). The level of endothelin-1 and nitrogen oxide metabolites in the blood plasma of patients was comparable between the first and second subgroups of observation during screening (p &gt; 0.05). After 12 months, there was a statistically significant decrease of Δ1% = -57.53 % endothelin-1 to 1.87 [1.44; 2.36] fmol/ml in the first subgroup and Δ2% = -82.34 % to 1.62 [1.37; 1.92] fmol/ml in the second subgroup. After 12 months of therapy in both subgroups, the level of total nitrogen oxide metabolites in blood plasma significantly increased Δ1% = 10.00 % to 21.00 [18.00 ; 23.00] mmol/l in the basic therapy subgroup, and Δ2% = 19.05 % to 24.00 [22.00; 26.00] mmol/l in the roflumilast subgroup, (p &lt; 0.05). A statistically significant difference in endothelin-1 levels and the amount of nitrogen oxide metabolites between subgroups was determined after 12 months of treatment.Conclusions. Among patients with COPD, endothelial dysfunction occurs, characterized by an increase in the concentration of endothelin-1 and a decrease in nitrogen oxide metabolites in the blood plasma. An increase in the level of endothelin-1 in blood plasma has a direct correlation with the value of the mean pulmonary artery pressure. Background therapy among patients with pulmonary hypertension on the background of COPD improves the state of endothelial function, with increased nitrogen oxide metabolites in the blood plasma. When added to background therapy, roflumilast significantly reduced the concentration of endothelin-1 in blood plasma.

Nocturnal blood pressure dipping as a marker of endothelial function and subclinical atherosclerosis in pediatric-onset systemic lupus erythematosus

BackgroundLoss of the normal nocturnal decline in blood pressure (BP), known as non-dipping, is a potential measure of cardiovascular risk identified by ambulatory blood pressure monitoring (ABPM). We sought to determine whether non-dipping is a useful marker of abnormal vascular function and subclinical atherosclerosis in pediatric-onset systemic lupus erythematosus (pSLE).MethodsTwenty subjects 9–19 years of age with pSLE underwent ABPM, peripheral endothelial function testing, carotid-femoral pulse wave velocity/analysis for aortic stiffness, and carotid intima-media thickness. We assessed the prevalence of non-dipping and other ABPM abnormalities. Pearson or Spearman rank correlation tests were used to evaluate relationships between nocturnal BP dipping, BP load (% of abnormally elevated BPs over 24-h), and vascular outcome measures.ResultsThe majority (75%) of subjects had inactive disease, with mean disease duration of 3.2 years (± 2.1). The prevalence of non-dipping was 50%, which occurred even in the absence of nocturnal or daytime hypertension. Reduced diastolic BP dipping was associated with poorer endothelial function (r 0.5, p = 0.04). Intima-media thickness was significantly greater in subjects with non-dipping (mean standard deviation score of 3.0 vs 1.6, p = 0.02). In contrast, higher systolic and diastolic BP load were associated with increased aortic stiffness (ρ 0.6, p = 0.01 and ρ 0.7, p < 0.01, respectively), but not with endothelial function or intima-media thickness.ConclusionIn a pSLE cohort with low disease activity, isolated nocturnal BP non-dipping is prevalent and associated with endothelial dysfunction and atherosclerotic changes. In addition to hypertension assessment, ABPM has a promising role in risk stratification and understanding heterogeneous mechanisms of cardiovascular disease in pSLE.

P0848PROSPECTIVE OPEN-LABEL EXPLORATIVE RANDOMISED SINGLE-CENTRE COMPARATIVE STUDY TO DETERMINE THE EFFECTS OF VARIOUS INTRAVENOUS IRON PREPARATIONS ON MARKERS OF OXIDATIVE STRESS AND KIDNEY INJURY IN CHRONIC KIDNEY DISEASE (IRON-CKD)

Abstract Background and Aims Iron deficiency is commonly treated with intravenous (IV) iron where oral iron is insufficient or cannot be tolerated. While IV iron is considered efficient and effective, safety concerns exist regarding the potential effect of IV iron on oxidative stress, inflammation and endothelial function. Transferrin is unable to saturate all the iron administered. Consequently, evidence has suggested differential generation of “free” or catalytic labile iron, depending on iron preparation. Labile iron stimulates lipid oxidation and free radical generation which can lead to increased oxidative stress, inflammation and endothelial dysfunction. The comparative risk of IV iron preparations has not been previ-ously extensively assessed. The possibility of IV iron leading to changes in oxidative stress, inflammation and endothelial function is assessed in this study. The potential interplay of IV iron changes with signaling pathways may lead to renal damage depending on the iron formulation used. This may lead to tubular and glomerular injury manifested as raised Neutrophil gelatinase-associated lipocalin (NGAL) levels in patients with chronic kidney disease (CKD). Method IRON-CKD is a prospective open-label explorative randomized, single-centre study assessing comparative safety and efficacy of three parenteral iron preparations. Patients with established CKD stages 3-5 and serum ferritin (SF) &amp;lt; 200microg/L and/or transferrin saturation (TS) &amp;lt;20% were recruited and randomized in a 1:1:1:1 ratio. The groups received a single infusion of 200mg Iron Dextran (Cosmofer ®), 200 mg Iron Sucrose (Venofer ®), and Iron Isomaltoside (Monofer ®) either as low (200mg) or high dose (1000mg). The patients were followed-up after IV iron at 2 hours and then at 1 day, 1 week, 1 month and 3 month intervals. Oxidative stress markers (Thiobarbituric acid reactive substances (TBARS)), inflammatory markers (Interleukin-1b, Interleukin-6, Interleukin-8, Interleukin-10) and surrogate markers of endothelial dysfunction (E-selectin, P-selectin) were measured. NGAL levels for establishment of potential acute kidney insult were measured. Free catalytic iron generation was also measured using the FeROS™ as-say. Data are presented as means and standard error of the mean (SEM). Statistical analysis was carried out using ANOVA. A p value of &amp;lt;0.05 was statistically significant. Results Forty patients were recruited and randomised with 10 per group. The mean age was 58.8 (±2.2) years and 23 (58%) were male. Free labile iron and TBARS increased within 2 hours of infusion (1.4 ΔFU/min (±0.5) to 7.4 ΔFU/min (±2.4)) (1083.0 nM (± 117.1) to 1552.6 nM (±156.0)) respectively with complete recovery within one week. TBARS and free labile iron were more pronounced within one day in the group receiving high dose Monofer® (TBARS: pre-infusion: 846.0 nM (±108.9) to 1865.0 nM (±203.2); Free labile iron: pre infusion: 0.3 ΔFU/min (±0.2) to 19.6 ΔFU/min (±7.1)). These were statistically significant with p &amp;lt; 0.001. These returned to pre-dosage levels and did not translate to any detriment in markers of inflammation or endothelial function (E-selectin or P-selectin). There was a non-statistically significant increase in Interleukin-10 (an anti-inflammatory cytokine) 2-hours post-infusion which was transient. Intravenous iron cumulatively and comparatively did not lead to a significant increase in NGAL (pre-infusion 570.5 ng/ml (±52.8); post-infusion 547.8 ng/ml (SEM: ±50.5); 3 months interval 534.8 ng/ml (±52.8)) at any given time point. Conclusion High dose of IV iron leads to a transient increased generation of free iron which disappears within one week. Iron therapy, at least in the short term, does not adversely affect markers of acute kidney injury, endothelial function, inflammation and oxidative stress status. This mechanistic data indicates that IV iron at both low and high doses is safe in patients with chronic kidney disease.

P0739PANEL OF SENSITIVE BIOMARKERS OF THE PRIMARY RESPONSE TO RENAL INJURY FOR AN EARLY DIAGNOSIS OF CHRONIC KIDNEY DISEASE

Abstract Background and Aims The identification of early kidney injury biomarkers is of utmost importance, since most widely used markers of kidney function vary only after several biological changes. Biomarkers allowing an earlier diagnosis of chronic kidney disease (CKD) would avoid delays in the treatment of patients. It is unlikely that a single marker is sufficient to detect the onset of CKD considering the multiple pathophysiological changes underlying primary renal response to renal injury. Several markers of inflammation, endothelial (dys)function, glomerular and tubulointerstitial injuries have been proposed and could be used combined as a panel of markers with different specificities, allowing an early detection of renal injury. Our aim was to study a panel of biomarkers proposed as early markers of renal injury, with different specificities, to evaluate and compare their sensitivities at different CKD stages. Method In this preliminary study, we enrolled 22 healthy individuals and 27 CKD patients separated into 3 groups, according to the CKD stage: 9 in stages 1 and 2; 9 in stage 3, and 9 in stages 4 and 5. None of the patients presented inflammatory, infectious or neoplastic diseases. Diagnosis and CKD stage assignment were performed according to KDIGO guidelines. We evaluated circulating levels of cystatin C (CystC), creatinine (Cr), beta trace protein (BTP) as markers of renal function; tissue inhibitor metalloproteinase 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL) and transforming growth factor-β (TGF-β) as markers of interstitial tubulointerstitial injury; asymmetric dimethylarginine (ADMA) and tissue plasminogen activator (t-PA), as markers of endothelial (dys)function; pentraxin 3 (PTX3), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as markers of inflammation; and, pro B-type natriuretic peptides (proBNP), as a marker of cardiac (dys)function. Results In early stages of CKD (1 and 2), we found significant changes in markers of renal function (BTP, but not Cr and CystC), of tubular interstitial injury (TIMP-1 and TGF-β), of inflammation (TNF-α), of endothelial (ADMA) and cardiac (proBNP) dysfunction (vs. controls). In stage 3, we found significant changes (vs. stages 1-2) in markers of renal function (Cr and CystC), inflammation (TNF-α, IL-6), endothelial dysfunction (t-PA) and tubulointerstitial injury (TIMP-1); in stages 4-5 (vs. stage 3), we found significant changes only in the classic marker, Cr, and a trend towards increased CystC. Moreover, we found that at stages 1-2 all patients showed higher levels of BTP and proBNP when compared to the median value in the control group; TIMP-1 and ADMA were increased in 7/9 patients; TNF-α was increased in 7/9 patients; and 7/9 patients had lower values of TGF-β compared to the median value of controls. For the classical markers, Cr and CystC, we found that 5/9 and 4/9 patients, respectively, had lower values than the median value of controls; however, only 2/9 patients showed abnormal creatinine values (vs. reference values). Conclusion Our data suggest that a panel including classic (Cr and CystC) and more sensitive blood markers of the primary response to renal injury (BTP, TIMP-1 or TGF-β, ADMA, TNF-α and proBNP) would allow an earlier diagnosis of CKD, avoiding a delay in diagnosis and management of CKD patients.

Predisposition to superimposed preeclampsia in women with chronic hypertension: endothelial, renal, cardiac, and placental factors in a prospective longitudinal cohort

ABSTRACT Objective To assess the contribution of maternal and placental factors to the development of superimposed preeclampsia in women with chronic hypertension. Methods Endothelial and renal function markers were serially assessed in 90 pregnant women with chronic hypertension and controls. Results Syndecan-1 concentrations were lower at 26–27+6 weeks in women with chronic hypertension who subsequently developed superimposed preeclampsia compared with those who did not. Decreased PlGF and raised urine albumin:creatinine ratio were also associated with development of superimposed preeclampsia. Conclusion Decreased syndecan-1 and PlGF concentrations implicate endothelial glycocalyx disturbance and reduced placental angiogenic capacity, respectively, in the pathophysiology of superimposed preeclampsia.

The Effect of Dietary Nitrate and Vitamin C on Endothelial Function and Oxidative Stress Biomarkers

Abstract Objectives Examine the effects of concentrated beetroot juice (CBJ) supplementation with and without vitamin C on markers of endothelial function (reactive hyperemia index (RHI) and blood biomarkers) and lipid profiles. Methods Subjects 50 to 70 years of age with low density lipoprotein (LDL) &amp;gt; 130 mg/dL and RHI ≤ 2 were enrolled in this randomized crossover double-blind study. Two 4-week interventions were separated by a 2-week washout. Subjects were assigned to daily CBJ (70 mls) with 1000 mg of vitamin C (NC) or CBJ with matched placebo (N), then switched to alternate treatment. At baseline and 4-weeks, RHI was measured using EndoPAT. Secondary outcomes included the sum of plasma NO metabolites (NO2 + NO3 = NOx), oxidized LDL (oxLDL), and serum lipids. Paired t-tests were used to compare differences between treatments. Results Eighteen of 23 subjects completed all study visits (7 male, 11 females). No significant treatment differences were observed in RHI change (N: 0.21 ± 0.46; NC: 0.20 ± 0.67; P &amp;gt; 0.05). NC subjects with baseline RHI of &amp;lt; 1.67 (mean = 1.23; n = 8) had greater improvements in RHI compared to subjects with RHI scores &amp;gt; 1.67 (mean = 1.75; n = 8; P = 0.02). Compared to N, NC resulted in a significant increase in plasma NOx (N: 94.2 ± 15.5 μmol/L; NC: 128.7 ± 29.1 μmol/L; P = 0.01). NC treatment reduced oxLDL/NOx ratio compared to N (N: −3.97 ± 2.8 U/L; NC: −4.29 ± 3.1 U/L; P = 0.02). NC elicited significant reductions in LDL (N: 2.2 ± 2; NC: −10.7 ± 23; P = 0.049), and triglycerides (N: 14.6 ± 43; NC: −43.7 ± 45; P = 0.03) with no change in serum high density lipoprotein. Conclusions NC appears effective at improving RHI in subjects with evidence of endothelial dysfunction. Four weeks of NC enriched the NO pool and promoted favorable changes in oxLDL/NOx ratio and blood lipids in subjects with hypercholesterolemia. These preliminary findings highlight a novel supplementation strategy that may reduce the progression of atherosclerotic disease and deserves further attention in studies using flow mediated dilation methods. Funding Sources Thornton Scholarship funds, College of Health Sciences, University of Kentucky.

Attenuation of Post-Meal Cardio-Metabolic Indices with Red Raspberries in Older Overweight/Obese Adults

Abstract Objectives Red raspberries (RRB) contain fiber and a unique combination of polyphenols with possible cardiovascular and metabolic benefits. The objective of this study was to evaluate the effects of acute red raspberry intake on cardio-metabolic markers of postprandial substrate metabolism and vascular endothelial function in older overweight/obese adults. Methods Thirty adults (age: 60 ± 4 years, BMI: 29.9 ± 3.0 kg m−2, mean ± SD) were randomized to the single-blinded, controlled, crossover trial. Participants consumed a high carbohydrate moderate fat breakfast (HCMF) meal containing 0 gram (control, 750 kcal) or 25 gram of freeze-dried RRB powder (2 cups fresh RRB equivalence, 752 kcal) on two occasions separated by 7 days washout period. Blood was collected at baseline and then again at 8 time points over 7.5 hours after test meals to determine glucose, insulin and triglyceride concentrations. Flow-mediated dilation (FMD) was assessed at baseline and then at 2 and 5 hours post test meal. Results A significant treatment * time interaction was observed for glucose (P = 0.014) and insulin (P &amp;lt; 0.01). Additionally, RRB significantly reduced the incremental area under the curve (iAUC) of insulin (P &amp;lt; 0.05), as well as the postprandial maximum concentration of glucose (P &amp;lt; 0.05), and insulin (P &amp;lt; 0.05). No significant treatment-related differences were observed for triglycerides. Vascular function as measured by changes in %FMD was significantly influenced by treatment (RRB 5.5 ± 0.3% versus control 4.7 ± 0.3%, P = 0.015). Conclusions Acute RRB supplementation attenuated postprandial glycemia and increased the vascular relaxation response after an HCMF meal challenge in a group of older overweight and obese individuals. Funding Sources This work was supported by the National Processed Raspberry Council.

No Difference in Lipemic Response or Endothelial Function Following Interesterified and Non-Interesterified Functionally Equivalent Fats: A Randomized Controlled Trial

Abstract Objectives Interesterified (IE) fats are now used as hard fats to replace harmful trans fats, however the cardiometabolic health impact of the most commonly consumed IE fat blends are unknown. The InterCardio study (NCT03438084) investigated the effect of the most commonly consumed IE spread versus functionally equivalent hard fats and a control oil, on postprandial lipemia (PPL) and acutely changing markers of endothelial function. Methods A four-armed, double blind, randomized controlled trial in healthy males and females (n = 50) aged 35–75 years compared sequential test meals (0 h; 897 kcal, 50 g fat, 16 g protein, 88 g carbohydrate, 5 h; 550 kcal, 30 g fat, 15 g protein, 39 g carbohydrate) on postprandial plasma triacylglycerol (TG) concentrations, endothelial function (flow mediated dilation (FMD)), plasma nitrite concentrations and NADPH oxidase activity. Test fats were: a commercially available IE spread, a functionally equivalent non-IE spread, spreadable butter (SB), and a high-MUFA oil (rapeseed oil) as control. Melt curve data for the spreadable fats showed similar solid fat content at 37°C (IE; 0.3%, non-IE; 0.4%, SB; 0%). Blood was collected at fasting and regular intervals up to 8 hrs, and FMD was measured at fasting, 4.5 hrs and 7.5 hrs. Results All 4 test fats increased TG levels postprandially, reaching peak concentrations at 6 hrs. There was no significant treatment or treatment x time effects on plasma TAG concentrations (P = 0.684), nor incremental areas under the curves up to 4 and 8 hrs; mean iAUC0–8 h (95% CI) were 5.4 mmol/L.h (4.3, 6.4) for IE spread, 5.7 mmol/L.h (4.3, 6.8) for non-IE spread, 5.5 mmol/L.h (4.0, 7.0) for SB and 5.9 mmol/L.h (4.3,6.8) for rapeseed oil. There were no significant treatment effects on endothelial function, while nitrite concentrations and NADPH oxidase activity reduced postprandially. Mean NAPDH oxidase activity following IE spread, non-IE spread, SB and rapeseed oil at 6 h were 322, 333, 270, and 268 respectively. Conclusions In the first study to investigate the acute effects of commercially relevant IE and non-IE spreads and SB, we report no adverse effect of IE fats on acutely changing cardiometabolic risk factors relative to a high-MUFA reference oil. The similar effects on endothelial function and postprandial lipemia is likely to be due to their similar solid fat content at body temperature. Funding Sources BBSRC.

Kidney and vascular function in adult patients with hereditary fructose intolerance

Objective: Previous studies have shown that patients with hereditary fructose intolerance (HFI) are characterized by a greater intrahepatic triglyceride content, despite a fructose-restricted diet. The present study aimed to examine the long-term consequences of HFI on other aldolase-B-expressing organs, i.e. the kidney and vascular endothelium.Methods: Fifteen adult HFI patients were compared to healthy control individuals matched for age, sex and body mass index. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (cf-PWV) and endothelial function by peripheral arterial tonometry, skin laser doppler flowmetry and the endothelial function biomarkers soluble E-selectin [sE-selectin] and von Willebrand factor. Serum creatinine and cystatin C were measured to estimate the glomerular filtration rate (eGFR). Urinary glucose and amino acid excretion and the ratio of tubular maximum reabsorption of phosphate to GFR (TmP/GFR) were determined as measures of proximal tubular function. Results: Median systolic blood pressure was significantly higher in HFI patients (127 versus 122 mmHg, p = .045). Pulse pressure and cf-PWV did not differ between the groups (p = .37 and p = .49, respectively). Of all endothelial function markers, only sE-selectin was significantly higher in HFI patients (p = .004). eGFR was significantly higher in HFI patients than healthy controls (119 versus 104 ml/min/1.73m2, p = .001, respectively). All measurements of proximal tubular function did not differ significantly between the groups.Conclusions: Adult HFI patients treated with a fructose-restricted diet are characterized by a higher sE-selectin level and slightly higher systolic blood pressure, which in time could contribute to a greater cardiovascular risk. The exact cause and, hence, clinical consequences of the higher eGFR in HFI patients, deserves further study.

The Effect of Circular Training Program on Endothelial-Derived Microparticles in Overweight Men

Objective: Aging is associated with endothelial dysfunction and arthrosclerosis. This study aimed to assesses the impact of combined circular training (resistance-interval) on endothelial-derived microparticles (EMPs) as a marker of endothelial function and cardiovascular risk factors in overweight elderly men. Materials and Methods: In this experimental study, twenty four overweight men aged 50 - 55 years were divided to exercise group (8 weeks circular training, 3 times/weekly, n= 12) and control group (no training, n= 12) by simple random sampling. The anthropometric measurements, serum EMPs and cardiovascular risk factors (triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), and high density lipoprotein (HDL)) were measured before and after training program in exercise and control groups. Data were analyzed by student’s T-test to assess the statistical significance of the changes. P -value less than 0.05 were considered statistically significant. Results: A significant decreases were observed in anthropometrical markers (weight, BMI, body fat percentage) by training program in exercise group ( P -value&lt; 0.001). Circular training induced significant decrease in EMPs ( P -value= 0.004), TG ( P -value= 0.020), TC ( P -value= 0.001) and increase in HDL ( P -value&lt; 0.001) compared to pre-training. No significant change was observed in LDL by circular training in exercise group ( P -value= 0.052). There were no changes in all dependent variables in the control subjects ( P value≥ 0.05). Conclusion: Based on these data, it is concluded that combined circular training can be improve endothelial function in overweight elderly men.

Effect of oral vitamin C ingestion on the vascular endothelial function and oxidative stress marker exposed to after transient heat-not-burn tobacco smoking

Effect of oral vitamin C ingestion on the vascular endothelial function and oxidative stress marker exposed to after transient heat-not-burn tobacco smoking

Effect of vitamin D3 supplementation on vascular and metabolic health of vitamin D–deficient overweight and obese children: a randomized clinical trial

Obese children are vulnerable to vitamin D deficiency and impaired cardiovascular health; vitamin D replenishment might improve their cardiovascular health. The aims were to determine, in vitamin D-deficient overweight and obese children, whether supplementation with vitamin D3 1000 or 2000 IU/d is more effective than 600 IU/d in improving arterial endothelial function, arterial stiffness, central and systemic blood pressure (BP), insulin sensitivity (1/fasting insulin concentration), fasting glucose concentration, and lipid profile and to explore whether downregulation of adipocytokines and markers of systemic inflammation underlies vitamin D effects. We conducted a randomized, double-masked, controlled clinical trial in 225 10- to 18-y-old eligible children. Change in endothelial function at 6 mo was the primary outcome. Dose-response increases in serum 25-hydroxyvitamin D concentrations were significant and tolerated without developing hypercalcemia. Changes at 3 and 6 mo in endothelial function, arterial stiffness, systemic-systolic BP, lipids, and inflammatory markers did not differ between children receiving 1000 or 2000 IU vitamin D and children receiving 600 IU. Some secondary outcomes differed between groups. Compared with the 600-IU group, central-systolic, central-diastolic, and systemic-diastolic BP was lower at 6 mo in the 1000-IU group [-2.66 (95% CI: -5.27, -0.046), -3.57 (-5.97, -1.17), and -3.28 (-5.55, -1.00) mm Hg, respectively]; insulin sensitivity increased at 3 and 6 mo and fasting glucose concentration declined at 6 mo (-2.67; 95% CI: -4.88, -0.46 mg/dL) in the 2000-IU group. Correction of vitamin D deficiency in overweight and obese children by vitamin D3 supplementation with 1000 or 2000 IU/d versus 600 IU/d did not affect measures of arterial endothelial function or stiffness, systemic inflammation, or lipid profile, but resulted in reductions in BP and fasting glucose concentration and in improvements in insulin sensitivity. Optimization of children's vitamin D status may improve their cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01797302.

The effect of vitamin E supplementation on biomarkers of endothelial function and inflammation among hemodialysis patients: A double-blinded randomized clinical trial

ObjectivesThe present study was aimed to investigate the effect of alpha-tocopherol supplementation on biomarkers of endothelial function (Intercellular Adhesion Molecule 1 and Vascular Cell Adhesion Protein 1) and inflammatory markers (Interleukin 6 and high-sensitivity C-reactive protein) among the hemodialysis patients. MethodsTo conduct this randomized, double-blinded, and placebo-controlled clinical trial, 49 hemodialysis patients, aged 20–60 years, were recruited and randomly divided into the intervention and control groups. The intervention group (n = 25) received 600 IU alpha-tocopherol soft gels (200 IU three times daily), while the controls (n = 24) consumed the identical placebo soft gels for 10 weeks. At the baseline and end of the study, 7 ml pre-dialysis blood samples were taken from all participants to measure their serum concentrations of ICAM-1, VCAM-1, IL-6, and hs-CRP. ResultsAlpha-tocopherol supplementation reduced the serum levels of ICAM-1 and VCAM-1 significantly (-140.67 ± 57.25 ng/ml vs. -15.97 ± 79.19 ng/ml, P = 0.001 for ICAM-1 and --6.79 ± 4.76 ng/ml vs. 1.02 ± 3.22 ng/ml, P = 0.019 for VCAM-1). However, no significant difference was observed between the two groups regarding the serum levels of hs-CRP (-0.15 ± 0.19 mg/l vs. 0.02 ± 0.12 mg/l; P = 0.32) and IL-6 (-0.03 ± 0.1 pg/ml vs. - 0.06 ± 0.11 pg/ml; P = 0.65). ConclusionsOur results showed that 10 weeks of supplementation with 600 IU alpha-tocopherol improved ICAM-1 and VCAM-1 levels, but did not have any effect on the serum concentration of IL-6 and hs-CRP in hemodialysis patients. Further studies are required to confirm these findings.

Increased arterial velocity pulse index is an independent factor related to skeletal muscle mass reduction and tissue damage in patients with cardiovascular disease.

Reduced skeletal muscle mass is the most important component of sarcopenia. Aging and chronic diseases, including chronic heart failure, are the causes of reduced skeletal muscle mass. However, little is known about the mechanism of skeletal muscle mass reduction in patients with cardiovascular disease (CVD). The purpose of this study was to assess the associations among skeletal muscle mass reduction, endothelial function, and other markers of advanced vascular damage in CVD patients. This was a retrospective cross-sectional analysis that included 310 inpatients with CVD in our hospital. Flow-mediated vasodilation (FMD) was performed to assess early vascular damage, i.e., endothelial dysfunction. The arterial velocity pulse index (AVI) and arterial pressure volume index (API) were assessed to reveal signs of advanced vascular damage, such as arterial stiffening and increased peripheral resistance. The bioelectrical phase angle (PA), as a marker of tissue damage, and the skeletal muscle index (SMI) were measured. Correlation analyses were performed among these parameters. Sarcopenia was diagnosed in 25.5% of patients according to the Asian Working Group for Sarcopenia criteria. Greater progression of arterial stiffness, shown by a higher AVI, and more severe tissue damage, shown by a narrower PA, were found in individuals with sarcopenia. Stepwise multivariate regression analysis showed that sex, age, PA, hypertension, and AVI were factors independently correlated with SMI. In conclusion, advanced vascular damage, such as increased arterial stiffness and peripheral resistance, might play an important role in the reduction in skeletal muscle mass, possibly through damage to skeletal muscle tissue in CVD patients.

MiR-20a ameliorates diabetic angiopathy in streptozotocin-induced diabetic rats by regulating intracellular antioxidant enzymes and VEGF.

We evaluated the beneficial effect of miR-20a mimic against diabetic angiopathy (DA) in rats by regulating intracellular antioxidant enzymes and vascular endothelial growth factor (VEGF). Diabetes was induced by intraperitoneal administration of streptozotocin (STZ; 65 mg/kg). Rats were then treated with miR-20a mimic (250 nmol/kg orally) for 8 weeks after STZ administration. The effect of miR-20a mimic against DA in rats was evaluated by estimating serum glucose concentration, lipid profile, Lp-a, kidney function test, inflammatory mediators, and markers of endothelial cell function. Markers of oxidative stress in the aortic tissue were estimated in rats treated with miR-20a mimic. Western blot assay, RT-PCR, and histopathology of kidney and myocardial tissues were also performed. Serum levels of blood glucose and markers of renal function were significantly lower, and the lipid profile improved in the miR-20a mimic group compared to the DA group. Treatment with miR-20a mimic ameliorated the altered markers of endothelial function and oxidative stress, as well as mediators of inflammation, in the DA rats. Protein expressions of ERK1/2, JNK, and p38 MAPK, as well as mRNA expressions of TLR-4 and NF-κB, in aortic tissues were lower in the miR-20a mimic group than in the DA group. The miR-20a mimic group had fewer histopathological changes in kidney and myocardial tissues than the DA group. MiR-20a mimic can protect against DA in rats by regulating vascular endothelial function and oxidative stress.

Effects of diet-induced weight loss on postprandial vascular function after consumption of a mixed meal: Results of a randomized controlled trial with abdominally obese men.

Effects of weight loss on postprandial vascular function have not been studied so far. We therefore examined (i) effects of diet-induced weight loss on postprandial changes in various vascular function markers after consumption of a mixed meal and (ii) differences between normal-weight and abdominally obese men of comparable age at baseline and after weight loss. Fifty-four apparently healthy abdominally obese (waist circumference: 102-110cm) and 25 normal-weight men (waist circumference: <94cm) participated. The abdominally obese men were randomly allocated to a diet-induced weight-loss program or a no-weight loss control group. Men assigned to the weight-loss program followed a calorie-restricted diet for six weeks targeting a waist circumference of less than 102cm, followed by a weight-maintenance period for two weeks. The control group maintained their habitual diet and physical activity levels. Measurements were performed before and two hours after consumption of the test meal consisting of two muffins (containing 56.6g fat) and 300mL low-fat milk. The mean weight loss was 10.3kg in the weight-loss compared with the control group. The postprandial change in flow-mediated vasodilation of the brachial artery (FMD) was significantly higher at baseline in normal-weight as compared with the postprandial change in abdominally obese men (1.89±2.52 versus 0.48±2.50 percentage points; P=0.027). However, no differences in postprandial changes were observed in the abdominally obese men after weight loss compared with the control treatment. Also, weight reduction did not affect postprandial changes in carotid-to-femoral pulse wave velocity, retinal microvascular caliber properties, or plasma markers of microvascular endothelial function. Even though postprandial increases in triacylglycerol (P=0.028), insulin (P=0.029) and C-peptide concentrations (P<0.001) were reduced in the abdominally obese men following weight loss, postprandial changes in FMD at the end of the weight-loss treatment were still more unfavorable as compared with those observed in normal-weight individuals. In this trial with abdominally obese men, we did not find effects of diet-induced weight loss on postprandial changes in vascular endothelial function, arterial stiffness and markers of microvascular function. This trial was registered on ClinicalTrials.gov under study number NCT01675401.

Cardiovascular, endothelial function, and immune markers in response to treatment with a polysaccharide in HIV+ adults in a randomized, double-blind placebo-control trial

Cardiovascular, endothelial function, and immune markers in response to treatment with a polysaccharide in HIV+ adults in a randomized, double-blind placebo-control trial