Markers Of Endothelial Function Research Articles

Anti-atherosclerotic and cardiovascular protective benefits of Brazilian nuts.

Brazil nuts are rich in magnesium, selenium, arginine and other amino acids, dietary fiber, tocopherols (vitamin E), phytosterols, linoleic acid, linolenic acid, sitosterols, monounsaturated and polyunsaturated fatty acids, polyphenols and other amino acids. Due to such a rich mixture of nutrients, Brazil nuts protect LDL from peroxidation, and improve endothelial function, blood pressure, lipid metabolism, and decrease endothelial inflammatory markers, DNA oxidation, and blood lipids (cholesterol, LDL, triglycerides). Here, we review and propose biological mechanisms by which bioactive compounds of Brazil nuts afford protections against atherosclerosis and cardiovascular diseases. Just a few nuts per day provide sufficient cardiovascular benefits, including protection against development and progression of atherosclerosis.

Effect on MicroRNA-92a in Atherosclerosis along with FlowMediated Vasodilation Study

Atherosclerosis has been regarded as an inflammatory disease. The vascular endothelium is considered as having multiple functions, regulating vascular tone, thrombosis, haematosis, permeability and cell adhesion. The emergence of microRNAs (miRNAs) as significant regulators of pathophysiological processes has indicated novel molecular insights and provided new therapeutic targets in atherosclerotic condition. Many studies have revealed that miRNA are associated with cardiovascular disease (CVD). With respect to miR-92a, miR -92a, a member of the miR-17 to miR-92 cluster, is expressed highly in endothelial cells (ECs) and regulated by shear stress. Both In vitro and vivo, miR-92a expression is highly induced in atheroprone regions compared with atheroresistant regions under disturbed flow (d-flow) condition. The clinical and experimental studies have suggested that inhibition of miR-92a can contribute to the improvement of endothelial dysfunction, inflammation, and oxidative stress in atherosclerosis. Recent reports showed that antimiR-92a as novel therapeutic options can be attributed to the endothelial cell autophagy and cardiomyocyte metabolism and that mechanistically, atherosclerotic status promote the packaging of functional miR-92a-3p into endothelial microvesicles, thereby promoting angiogenic response into recipient endothelial cells. It is strongly suggested that miR-92a-3p, having novel biological function and mechanism is a potent therapeutic target in atherosclerosis-related diseases. It is putative that flow-mediated vasodilation (FMD) study, early surrogate marker of endothelial function may in part reflect miR-92a, multifunctional biomarker

A study of endothelial function by flow-mediated vasodilatation in patients with metabolic syndrome

Background: Metabolic syndrome (MetS) is characterized by clustering of cardiovascular risk factors.Endothelial dysfunction is the key early event in atherogenesis that occurs long before structural atherosclerotic changes and promotes cardiovascular events. The assessment of endothelial function by flow-mediated dilation (FMD) of the brachial artery has been proposed as a non-invasive marker for cardiovascular risk. Aim: Assessment of flow mediated vasodilatation of brachial artery as a non invasive marker of endothelial function in metabolic syndrome and To assess the relationship of number of risk factors in metabolic syndrome with endothelial dysfunction. Methodology: A case control study in which 50 patients with Metabolic Syndrome as per new IDF criteria and 50 controls were studied. Detailed clinical history, examination and Blood investigations like Fasting blood glucose, fasting lipid profile and ECG was done for every patients. Endothelial function was assessed by brachial artery flow mediated vasodilatation. Results: In the present study 100 (50 cases and 50 controls) patients were studied, males (54%) and females (46%), majority in the age group between 40-60 years (mean age - 49.76 ± 13.76yrs in cases and 44.94 ± 16.09 years among controls). We identified a significant difference between cases and age- and sex-matched controls regarding brachial artery FMD% (7.24 ± 5.24 and 21.29 ± 9.29 respectively; P value-0.000). Negative corelations were found between FMD% and various variables and also between number of components and FMD% (r = -0.239). Conclusion: MetS is associated with endothelial dysfunction as evidenced by decreased FMD% compared to controls. There is a negative correlation between various components of MetS, number of components of MetS and FMD%.

Phenotypic features of vascular calcification in chronic kidney disease.

Patients with chronic kidney disease stage 5 (CKD5) are predisposed to vascular calcification (VC), but the combined effect of factors associated with VC was sparsely investigated. We applied the relaxed linear separability (RLS) feature selection model to identify features that concomitantly associate with VC in CKD5 patients. Epigastric arteries collected during surgery from living donor kidney transplant recipients were examined to score the histological extent of medial VC. Sixty-two phenotypic features in 152 patients were entered into RLS model to differentiate between no-minimal VC (n=93; score 0-1) and moderate-extensive VC (n=59; score 2-3). The subset of features associated with VC was selected on the basis of cross-validation procedure. The strength of association of the selected features with VC was expressed by the absolute value of 'RLS factor'. Among 62 features, a subset of 17 features provided optimal prediction of VC with 89% of patients correctly classified into their groups. The 17 features included traditional risk factors (diabetes, age, cholesterol, BMI and male sex) and markers of bone metabolism, endothelial function, metabolites, serum antibodies and mitochondrial-derived peptide. Positive RLS factors range from 1.26 to 4.05 indicating features associated with increased risk of VC, and negative RLS factors range from -0.95 to -1.83 indicating features associated with reduced risk of VC. The RLS model identified 17 features including novel biomarkers and traditional risk factors that together concomitantly associated with medial VC. These results may inform further investigations of factors promoting VC in CKD5 patients.

Malnutrition impairs mitochondrial function and leukocyte activation

BackgroundThe aim of this study was to evaluate markers of inflammation, oxidative stress and endothelial function in a disease-related malnutrition (DRM) outpatient population.MethodsFor this cross-sectional study, a total of 83 subjects were included and clustered in 3 groups: 34 with normonutrition (NN), 21 with DRM without inflammation (DRM-I) and 28 with DRM and inflammation (DRM + I). Nutritional diagnosis was conducted for all subjects according to ASPEN. Biochemical parameters, proinflammatory cytokines, reactive oxygen species production, glutathione, mitochondrial membrane potential, oxygen consumption, adhesion molecules and leukocyte-endothelium interactions were evaluated.ResultsDRM + I patients showed lower albumin, prealbumin, transferrin, and retinol-binding protein levels with respect to the NN group (p < 0.05), differences that were less noticeable in the DRM-I group. DRM + I was associated with a significant increase in hsCRP and IL6 vs the NN and DRM-I groups, and TNFα was increased in both DRM vs NN. DRM was characterised by increased oxidative stress, which was marked by a significant increase in ROS levels and a decrease in mitochondrial membrane potential in the DRM + I group. An evident reduction in mitochondrial oxygen consumption and glutathione concentration was observed in both DRM groups, and was accompanied by increased leukocyte adhesion and adhesion molecules and decreased rolling velocity in the DRM + I group. Furthermore, percentage of weight loss was negatively correlated with albumin, prealbumin, transferrin, O2 consumption, glutathione and leukocyte rolling velocity, and positively correlated with hsCRP, IL6, TNFα, ROS, leukocyte adhesion, and VCAM-1.ConclusionsOur results show that DRM is associated with oxidative stress and an inflammatory state, with a deterioration of endothelial dysfunction in the DRM + I population.

Association between Upper-airway Surgery and Ameliorative Risk Markers of Endothelial Function in Obstructive Sleep Apnea

The objective of our study was to evaluate the effects of upper-airway surgery on improvement of endothelial function-related markers in patients with obstructive sleep apnea (OSA). Subjects with moderate to severe OSA who underwent upper-airway surgery, with a follow-up duration of at least 6 months, were included. Pre- and postoperative polysomnographic variables and endothelial function-related markers were compared. Subgroup and correlation analyses were conducted to find possible indicators for better endothelial function-related markers after upper-airway surgery. In total, 44 patients with OSA were included. The mean follow-up duration was 1.72 ± 0.92 years. Serum VEGFA [−20.29 (CI: −35.27, −5.31), p < 0.05], Ang2 [−0.06 (CI: −0.16, 0.03), p < 0.05], E-selectin [−7.21 (CI: −11.01, −3.41), p < 0.001], VWF [−58.83 (CI: −103.93, −13.73), p < 0.05], VWFCP [−33.52 (CI: −66.34, −0.70), p < 0.05], and TM [−0.06 (CI: −0.09, −0.03), p < 0.05] were significantly lower after upper-airway surgery. However, other risk markers of endothelial function, such as Ang1, ICAM1, VEGFR1, and VCAM, did not change significantly. Correlations between improved endothelial function-related markers and ameliorated oxyhemoglobin saturation and glucolipid metabolism were established. Upper-airway surgery might be associated with an improvement in endothelial function in patients with OSA. These changes may be associated with improved oxygen saturation after upper-airway surgery.

Inflammatory and cardiovascular diseases biomarkers in chronic hepatitis C virus infection: A review.

Hepatitis C virus (HCV) infects 180 million people worldwide and over 4 million people in the United States. HCV infection is a major cause of chronic liver disease and is recognized as a risk factor for clinical cardiovascular disease (CVD). Many studies have shown increased prevalence of cardiac and inflammatory biomarkers in patients with chronic HCV infection (CHC), and though these markers may be used to risk stratify people for cardiac disease in the general population their role in the HCV population is unknown. Patients with CHC have elevated cardiac and inflammatory biomarkers compared to noninfected controls which may play a role in CVD risk stratification. We undertook a systematic review of inflammatory and cardiac biomarkers in people with HCV infection with a focus on the effect of CHC on serum levels of these markers and their utility as predictors of CVD in this population. Medline, EMBASE, and Cochrane databases were searched for relevant articles until June 2019. A total of 2430 results were reviewed with 115 studies included. Our review revealed that HCV infection significantly alters serum levels of markers of inflammation, endothelial function, and cardiac dysfunction prior to HCV treatment, and some of which may change in response to HCV therapy. Current risk stratification tools for development of CVD in the general population may not account for the increased inflammatory markers that appear to be elevated among HCV‐infected patients contributing to increased CVD risk.

Effect of α-linolenic acid on vascular function and metabolic risk markers during the fasting and postprandial phase: A randomized placebo-controlled trial in untreated (pre-)hypertensive individuals.

Only a limited number of studies have examined the vascular and postprandial effects of α-linolenic acid (ALA, C18:3n-3). Therefore, we performed a well-controlled trial focusing specifically on the effects of ALA on vascular function and metabolic risk markers during the fasting and postprandial phase in untreated (pre-)hypertensive individuals. In a double-blind randomized, placebo-controlled parallel study, 59 overweight and obese adults (40 men and 19 women, aged 60±8 years) with a high-normal blood pressure or mild (stage I) hypertension consumed daily either 10g of refined cold-pressed flaxseed oil, providing 4.7g ALA (n=29), or 10g of high-oleic sunflower (control) oil (n=30) for 12 weeks. As compared with the high-oleic oil control, intake of flaxseed oil did not change brachial artery flow-mediated vasodilation, carotid-to-femoral pulse wave velocity, retinal microvascular calibers and plasma markers of microvascular endothelial function during the fasting and postprandial phase. Fasting plasma concentrations of free fatty acid (FFA) and TNF-α decreased by 58μmol/L (P=0.02) and 0.14pg/mL (P=0.03), respectively. No differences were found in other fasting markers of lipid and glucose metabolism, and low-grade systemic inflammation. In addition, dietary ALA did not affect postprandial changes in glucose, insulin, triacylglycerol, FFA and plasma inflammatory markers after meal intake. A high intake of ALA, about 3-5 times the recommended daily intake, for 12 weeks decreased fasting FFA and TNF-α plasma concentrations. No effects were found on other metabolic risk markers and vascular function during the fasting and postprandial phase in untreated high-normal and stage I hypertensive individuals.

B lymphocyte stimulator modulates number and function of endothelial progenitor cells in systemic lupus erythematosus

BackgroundCirculating endothelial progenitor cells (EPCs) are biologic markers of endothelial function. In patients with systemic lupus erythematosus (SLE), the numerical reduction and functional impairment of EPCs contribute to the endothelial dysfunction.Through ex vivo and in vitro studies, we aimed at evaluating the effects of B lymphocyte stimulator (BLyS) on EPC colonies and endothelial cells and also investigating BLyS receptor expression on these cells.MethodsEPCs were isolated from peripheral blood mononuclear cells (PBMC). In order to evaluate their ability to form colonies, EPCs were cultured on fibronectin-coated dishes and incubated with BlyS alone or BlyS and belimumab. Apoptosis of EPCs and endothelial cell line EA.hy926 was evaluated after 6, 12, and 24 h of incubation with BLyS and after 6 h with BLyS and belimumab. The expression of B cell activating factor-receptor (BAFF-R), B cell maturation antigen (BCMA), and transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI) on EPCs and EA.hy926 was analyzed by cytofluorimetry.ResultsThe number of EPC colonies was lower in patients than in controls. Moreover, the colonies from SLE patients were poorly organized compared to controls; the addition of belimumab restored the colony structure. Incubation with BLyS induced apoptosis of EPCs and EA.hy926 that was inhibited by the co-incubation with belimumab. BAFF-R and BCMA were expressed on both EPCs and EA.hy926, while TACI was expressed only on EPCs.ConclusionsEPCs and endothelial cells preferentially express BAFF-R which could be involved in the pro-apoptotic effect of BlyS. Belimumab administration seems to restore the quantitative and qualitative changes of EPC colonies both ex vivo and in vitro.

Influence of smoking and smoking cessation on biomarkers of endothelial function and their association with mortality

Background and aimsEndothelial dysfunction precedes atherosclerosis and smoking is a well-known risk factor for the development of endothelial dysfunction. The aim of our study was to analyse the effect of smoking on circulating markers of endothelial function and to investigate whether such effects have an influence on the potential use of these markers to estimate cardiovascular risk. MethodsStratified for smoking, levels of sE-/sP-/sL-selectin, von Willebrand (vWF), sICAM-1 and sVCAM-1, their association with mortality using Cox regression, and their accuracy of risk prediction using area-under-the-ROC-curve and net-reclassification-index were analysed in 1926 participants from the Ludwigshafen Risk and Cardiovascular Health (LURIC) – a prospective case-control study in patients who underwent coronary angiography with a median mortality follow-up of 10.6 years. ResultsIn smokers, higher concentrations of sICAM-1, sE-selectin sP-selectin, but lower concentrations of sL-selectin and sVCAM-1, were detected compared to never-smokers. A direct association with mortality was found for levels of sICAM-1, sVCAM-1 and vWF regardless of smoking. Low sL-selectin levels were inversely associated with mortality in heavy and light smokers, with hazard ratios of 0.72 and 0.67 per 1-SD increase, adjusted for cardiovascular risk factors. Adding sL-selectin to a model based on traditional risk factors significantly improved AUC from 0.725 to 0.752 (p = 0.034) with an NRI of 43% (16.9%–62.3%). ConclusionsSmoking alters the concentration of circulating markers of endothelial function. sL-selectin is decreased in smokers, inversely associated with risk, and could be a useful marker to improve risk prediction.

The effects of sampling from a peripheral venous catheter compared to repeated venepunctures on markers of coagulation, inflammation, and endothelial function

Peripheral venous (PV) catheters are often used for serial blood sampling, but studies suggest that PV catheters increase markers of coagulation activation and inflammation. Whether the increase is caused by irritation of the vessel wall or diurnal variation is unknown. We therefore compared the effects of a PV catheter and repeated venepunctures on markers of coagulation, inflammation, and endothelial function.A PV catheter was inserted at 07:45 in a hand vein in 10 healthy subjects, and blood samples were collected at 8:00, 10:00, 12:00, and 14:00. In the contralateral arm, blood was simultaneously obtained by venepunctures. Measures of coagulation, i.e., activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin (TAT), inflammation, i.e., interleukin 6 (IL-6) and C-reactive protein (CRP), and endothelial function, i.e., plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), von Willebrand factor (vWF), and tissue factor (TF) were measured in plasma.The concentrations of TAT and F1 + 2 were significantly increased (10:00; p < .01, 12:00; p < .05, and 14:00; p < .01) in PV catheter samples compared with venepuncture samples. There was a minor increase in PT and INR and no increase in APTT, fibrinogen, CRP, PAI-1, tPA, vWF, and TF, with no differences between sampling methods. IL-6 concentrations increased in many PV catheter samples and venepuncture samples, but the response varied between the subjects.Blood collection through a PV catheter induces coagulation activation, whereas endothelial function is not affected. More studies are needed to disclose the effect of blood sampling on IL-6.

Genetics and inflammatory profile in tobacco dependence

Abstract The state of health of the population is determined by a set of factors belonging to human biology, environment, behaviors, and the health system (preventive, curative, and rehabilitative). Any of these factors can alter both individual and community health. The primary reason for tobacco dependence is nicotine addiction. Dopamine is released from the neurons located in the mesolimbic system. Nicotine stimulates the release of dopamine from these receptors. The genetic determination of nicotine dependence is determined by the subtypes of nicotine acetylcholine receptors (nAChRs) and conditioned by chromosome mutations at chromosomes 15q25.1, 8p11.21 or 20q13.12-q13.32. Low-amplitude systemic inflammation is demonstrated in all smokers and is confirmed by elevated levels of C-reactive protein, fibrinogen, Interleukin-6, and increased leukocyte levels. Moreover, coagulation and endothelial function markers such as hematocrit, plasma or blood viscosity, D-dimers, circulating adhesion molecules, tissue plasminogen activator, have also modified values in smokers.

2229Apoptotic and non-apoptotic circulating microparticles in patients with acute coronary syndromes

Abstract Background Circulating microparticles (MP) are surrogate biomarkers of atherosclerosis but their role in patients with acute coronary syndromes (ACS) remain unknown. Purpose To explore the levels of apoptotic and non-apoptotic MP in patients with ACS. Methods We enrolled a total of 153 patients as follows: 49 patients with STEMI, 35 NSTEMI, 38 with unstable angina (UA), 15 with stable CAD (SCAD) and 16 non-CAD (controls). Flow cytometry analysis was used to quantify circulating apoptotic (annexin+) and non-apoptotic endothelial cell (EMP), red blood cell (RMP) and platelet (PMP) derived microparticles. Circulating C-reactive protein (hsCRP) levels and cardiac troponin I (cTnI) were also assessed. Brachial FMD was also determined as a marker of endothelial function. Results There was a stepwise increase in the total number of EMP, RMP and PMP in patients with ACS (STEMI/NSTEMI) compared to UA, SCAD and non-CAD patients. This was mainly explained by the increase in the number of apoptotic EMP, RMP and PMP (a-c), while there were no significant differences in the level of apoptotic EMP, RMP or PMP between patient subgroups (not shown). There was no association between circulating levels of apoptotic or non-apoptotic EMP, RBP or PMP with hsCRP (p=NS for all). Apoptotic EMP only were negatively associated with brachial FMD (rho=−0.185, p=0.04) and positively with cTnI levels (rho= 0.307, p&lt;0.0001). Conclusions Circulating apoptotic (but not non-apoptotic) MP are increased in patients with ACS. A negative association is observed between the numbers of circulating apoptotic EMP only and systemic endothelial function. The biological role of circulating apoptotic microparticles' in the pathogenesis of ACS merits further investigation.

P709Improvement in endothelial function and arterial elastic properties facilitates response to cardiac resynchronization therapy

Abstract Background Cardiac resynchronization therapy (CRT) is a well-established therapy in heart failure (HF) patients with prolonged QRS. In HF patients, reduced nitric oxide availability and increased oxidative stress promote endothelial dysfunction (ED) and arterial stiffness. Purpose To investigate the pathophysiologic changes in endothelium and arterial elastic properties in CRT patients and their correlation to therapy. Methods We studied 32 HF patients before and 3 months after CRT implantation. In each visit we performed a 12-lead ECG and assessed markers of endothelial function. Specifically, we examined flow-mediated dilatation of the brachial artery (FMD), carotid to femoral pulse wave velocity (cfPWV), as well as the layer of endothelial glycocalyx using the Perfused Boundary Region (PBR) of the sublingual microvessel range: 5–25 microns. We also evaluated left ventricle ejection fraction (LVEF), left ventricle (LV) global longitudinal strain (GLS) and arterial elastance (Ea) to ventricular elastance (Ees) ratio (Ea/Ees) by echocardiography. Results 32 HF CRT patients, at age 65.5 (±10.9) years, with reduced LVEF (baseline LVEF: 27±7%, LVESV: 151±42 ml, GLS: 6.47±2.89%) were followed-up for a median of 115 days (IQR: 36). During follow up, all markers of ED demonstrated significant change: FMD was increased by 4.37±3.34% (p&lt;0.001), cfPWV and PBR 5–25 were reduced by 1.10±1.56 (p=0.003) and 0.13±0.25 microns (p=0.028) respectively. LVEF was significantly increased (mean change: 7.50±4.77%) and LVESV was significantly reduced (mean change: −26.91±17.20 ml). 16 of 32 patients were responders (LVESV change ≥15% compared to baseline). Among the changes of the examined markers during follow-up, response to CRT correlated with the change of FMD (OR: 3.10, 95% CI: 1.47–15.51, p=0.039) and change of Ea/Ees (OR: 0.000, 95% CI: 0.000–0.061, p=0,0239). Effect of change in measurements during follow-up on response to CRT Measurement OR (95% CI) Main effect p-value FMD change 3.100 (1.470–15.513) 0.0397 cfPWV change 0.669 (0.295–1.354) 0.0622 PBR 5–25 change 1.773 (0.008–455.458) 0.828 Ea/Ees change 0.000 (0.000–0.061) 0.0239 Conclusion Improvement in endothelial function and arterial elastic properties evaluated by FMD and Ea/Ees respectively are related with effective CRT.

P638High intensity interval exercise training improves endothelial function in patients with heart failure with preserved ejection fraction

Abstract Background Cardiac rehabilitation has traditionally invoved low-to moderate intensity continuous exercise training (MICT). There is growing evidence that high intensity interval exercise training (HIIT) shows similar or greater efficacy compared with MICT. However, the relationship between the training modality and its effects on endothelial function still remains to be elucidated. Purpose To evaluate the impact of high intensity interval exercise training versus low-to moderate intensity continuous exercise training on circulating blood markers of endothelial function: the stable end product of nitric oxide (NOx), S–nitrosothiols (RSNO–reservoir for bioavailable nitric oxide), dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) in patients (pts) with heart failure with preserved ejection fraction (HFpEF). Methods A total of 43 pts with HFpEF (mean age 57.5±6.8y) admitted at residential rehabilitation center were enrolled in the study. Patients were randomized to HIIT, (HIIT group, n=20) and MICT, (MICTgroup, n=23). At baseline and 3 weeks later, in all pts values of NOx, RSNO, ADMA and SDMA were determined and exercise test was performed. Results After 3 weeks NOx increased significantly in both groups: in HIITgroup (from 34.7±7.5 to 48.5±8.3 μmol/l, P&lt;0.0001), in MICTgroup (from 35.0±9.5 to 42.5±10.0 μmol/l, P&lt;0.05), and value of NOx after 3 weeks was higher in HIIT than in MICT group (P&lt;0.05). Value of ADMA as well of SDMA decreased in both groups after 3 weeks, and this decrease was significant in HIIT group: ADMA in HIIT group (from 0.305±0.055 to 0.250±0.077 μmol/l, P&lt;0.005) and in MICT group (from 0.325±0.069 to 0.280±0.140 μmol/l, ns); SDMA in HIIT group (from 0.285±0.050 to 0.240±0.060 μmol/l, P&lt;0,005) and in MICT group (from 0.270±0.080 to 0.247±0.063 μmol/l, ns). Value of RSNO significantly increased in both groups, with higher increase in HIIT group: in HIIT group (from 3.0±1.5 to 5.1±1.7 μmol/l, P&lt;0.001), in MICTgroup (from 3.2±1.7 to 4.5±2.3 μmol/l, P&lt;0.05). Compared to the baseline, at the end of the study, exercise capacity (METs) was significantly higher in both groups (P&lt;0.0001). Higher increase in METs in HIIT group during exercise training (by 39.8%), compared to increase in MICT group (by 27.2%), resulted in significantly higher exercise tolerance in HIIT than in MICT group at the end of the study (P&lt;0.02). In both groups, adverse events during or after exercise training, were not occurred. Conclusions In pts with HFpEF high intensity interval exercise training as well as low-to moderate intensity continuous exercise training induced favorable modification of endothelial function, expressed through increase of NOx and RSNO, and decrease of ADMA and SDMA. More significant increase of NOx and RSNO, and significant decrease of ADMA and SDMA gives an advantage to HIIT over MICT exercise training in patients with HFpEF.

Correlation of serum endothelin-1 with relapses of surgical treatment of diabetic maculopathy in type 2 diabetes mellitus

Introduction. In type 2 diabetes mellitus (T2DM), a cascade of pathological reactions unfolds in the vas­­cular endothelium, which, in turn, is included in the pathogenesis mechanisms and causes the develop­­ment of complications. The main marker of endothelial function is its hormone — endothelin-1 (ET1). The aim of the study was to establish the relation­ship between serum ET1 and relapses in the surgical treatment of diabetic maculopathy (DMP) using various options for vitreoretinal interventions in patients with TD2M. Material and methods. We observed 313 patients T2DM (313 eyes) with DMP and initial (group 1; n = 40), moderate or severe non-proliferative (NPDR; group 2; n = 92) and proliferative diabetic retinopathy (PDR; group 3; n = 181). The severity of retinopathy and DMP was determined in accordance with the recom­men­dations of the American Academy of Ophthalmology (2002). In this study, patients underwent four types of surgical interventions: 78 patients (78 eyes) underwent a three-port closed subtotal vitrectomy; 85 patients (85 eyes) — closed subtotal vitrectomy with peeling of the retina inner border membrane; 81 patients (81 eyes) — closed subtotal vitrectomy with peeling of the retina inner border membrane in combination with panretinal laser coagulation; 69 patients (69 eyes) — closed subtotal vitrectomy with peeling of the retina inner border membrane and panretinal laser coagu­lation in combination with cataract phacoemulsifica­­tion. In pa­­tients before surgery, serum ET1 levels were determined by enzyme-linked immunosorbent assay. The control group consisted of 95 people. For statistical processing of the obtained data, Statistica 10 software (StatSoft, Inc., USA) was used. Results and discussion. In patients with DMP serum ET1 level was many times higher: in group 1 it exceeded the control by 2.9 times, in group 2 — by 3.7 times and in group 3 — by 4.6 times (p < 0.001). The initial ET1 level did not differ with different methods of surgical intervention; there was also no statistical difference between the serum ET1 in each group with different treatment methods (p > 0.5). Serum ET1 level was higher in patients of group 1 with the presence of relapses, compared with patients of the same group who didn’t have relapses (by 1.4 times; p < 0.001). In patients of the remaining groups, there was no such difference (p > 0.2), thus, the level of ET1 was important for the formation of relapses only for patients with initial NPDD. Serum ET1 level was also higher in pa­­tients who had early persistent relapses (p < 0.001), which related to moderate and severe NDPR and PDR. Conclusion. The results showed a correlation bet­­ween the serum level of ET1 and the occurrence of early sustained relapses in the surgical treatment of DMP in patients with T2DM.

Endothelial and Autonomic Dysfunction at Early Stages of Glucose Intolerance and in Metabolic Syndrome.

This study evaluated sE-selectin, Endothelin-1, and cardiovascular autonomic neuropathy (CAN) at early stages of glucose intolerance and in metabolic syndrome (MetS). A total of 87 subjects - 39 males, of mean age 45.7±11.6 years and mean BMI 31.4±6.6 kg/m2, divided according to glucose tolerance and the presence of MetS were enrolled. Glucose tolerance was studied during OGTT. Anthropometric indices, blood pressure, HbA1c, lipids, hsCRP, sE-selectin, Endothelin-1, and immunoreactive insulin were measured. Body composition was assessed by a bioimpedance method (InBody 720, BioSpace). Tissue AGEs accumulation was evaluated by skin autofluorescence (AGE-Reader, DiagnOpticsTM). CAN was assessed by ANX-3.0 technology. In the groups, according to glucose tolerance, the prevalence of CAN was 5.7% in normal glucose tolerance (NGT), 8.6% in prediabetes, and 23.5% in newly diagnosed type 2 diabetes (NDD). In the groups, according to the presence of MetS, the prevalence of CAN was 12.3% in those with MetS and 4.8% in those without MetS. Parasympathetic activity was diminished at rest (p=0.048, 0.015, respectively) in NDD as compared to prediabetes and NGT; and there was a numerically elevated heart rate at rest in NDD in comparison to NGT. There was a negative correlation between parasympathetic tone and waist circumference, BMI, and visceral and total fat. There was no difference in the measured endothelial function markers in the groups according to glucose tolerance and MetS. sE-selectin correlated with HOMA-IR (r=0.275, p=0.048). No association between Endothelin-1 levels and assessed metabolic parameters was observed. There is a high prevalence of CAN at early stages of glucose intolerance and in MetS, due to decreased parasympathetic activity. Slight elevation of glycemia and MetS probably do not affect endothelial function, since sE-selectin seems to be related to insulin resistance.

Evaluating the reactivation of herpesviruses and inflammation as cardiovascular and cerebrovascular risk factors in antiretroviral therapy initiators in an African HIV-infected population (RHICCA): a protocol for a longitudinal cohort study

IntroductionIn Sub-Saharan Africa, the rising rates of cerebrovascular and cardiovascular diseases (CBD/CVD) are intersecting with an ageing HIV-infected population. The widespread use of antiretroviral therapy (ART) may confer an additive...

Addition of marine omega-3 fatty acids to statins in familial hypercholesterolemia does not affect in vivo or in vitro endothelial function

Prestatin trials reported positive effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) in cardiovascular disease, whereas recent studies and meta-analyses have not reproduced these results. The effect of n-3 PUFA in patients with familial hypercholesterolemia (FH), a group with particularly high risk of cardiovascular disease, is not well established. We investigated the effect of n-3 PUFA in the early stage of atherosclerosis in FH patients by evaluating invivo (peripheral arterial tonometry [PAT]) and invitro (plasma asymmetric dimethylarginine and E-selectin) endothelial function. This was a double-blind, placebo-controlled cross-over study with 34 FH patients on statin treatment (mean age 46.6years). In random order, all individuals were treated for 3 months with high-dose n-3 PUFA (2g, ×2) and 3 months placebo (olive oil, 2g ×2), separated by a 3-month washout period. Anthropometric data, blood samples, and PAT were collected at 4 time points. There were no significant changes in reactive hyperemia index measured by PAT after n-3 PUFA compared with placebo, median reactive hyperemia index after n-3 PUFA was 1.98 and after placebo 1.96 (P=.51). No significant changes were detected in the soluble endothelial marker asymmetric dimethylarginine (in 2 different assays) when comparing n-3 PUFA and placebo (P=.92 and .14, respectively). Finally, the level of E-selectin did not change significantly during the trial (P=.26). Addition of n-3 PUFA to standard lipid-lowering treatment in genetically verified FH patients did not affect the invivo endothelial function or soluble endothelial markers.

Gene Expression and Cardiometabolic Phenotypes of Vitamin D-Deficient Overweight and Obese Black Children.

Associations between whole blood transcriptome and clinical phenotypes in vitamin D-deficient overweight and obese children can provide insight into the biological effects of vitamin D and obesity. We determined differentially expressed genes (DEGs) in relation to body mass index (BMI) in vitamin D-deficient black children with a BMI ≥ 85th percentile and ascertained the cardiometabolic phenotypes associated with the DEGs. We examined whole-blood transcriptome gene expression by RNA sequencing and cardiometabolic profiling in 41, 10- to 18-year-old children. We found 296 DEGs in association with BMI after adjusting for age, race, sex, and pubertal status. Cardiometabolic phenotypes associated with the BMI-related DEGs, after adjusting for age, sex, pubertal status, and %total body fat, were (i) flow-mediated dilation (marker of endothelial function), (ii) c-reactive protein (marker of inflammation), and (iii) leptin (adipocytokine). Canonical pathways of relevance for childhood obesity and its phenotypes that were significantly associated with the BMI-related DEGs affected immune cell function/inflammation, vascular health, metabolic function, and cell survival/death; several immune and inflammatory pathways overlapped across the three phenotypes. We have identified transcriptome-based biomarkers associated with BMI in vitamin D-deficient, overweight and obese black children. Modulating effects of vitamin D supplementation on these biomarkers and their related phenotypes need further exploration.