Early Marker Of Endothelial Dysfunction Research Articles

THE SEVERITY OF VASCULAR INFLAMMATION AND ITS RELATIONSHIP WITH CLINICAL AND FUNCTIONAL FEATURES IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE WITHOUT CONCOMITANT CARDIOVASCULAR PATHOLOGY

The Russian Federation is one of the countries with a high prevalence of chronic obstructive pulmonary disease (COPD). In the last decade, the list of families of chemical regulators of vascular inflammation in COPD has been supplemented with information about growth factors, whose participation in the processes of regulation of vascular function seems significant. The study of the role of angiogenesis factors in patients with isolated COPD disease is insufficient at this stage and needs to be clarified. Objective. To study was to identify diagnostic and prognostic criteria for the severity of vascular inflammation and to assess its relationship with clinical and functional features in patients with COPD without concomitant cardiovascular pathology in comparison with the clinical phenotype of the disease. Material and methods. 96 patients with COPD were examined, the median age was 61 years. In addition to standard clinical, functional and laboratory research methods, the severity of vascular inflammation was assessed in all examined patients with the determination of quantitative indicators of human platelet growth AA factor and tumor necrosis factor-α (TNFα) by quantitative solid-phase enzyme immunoassay Results. In all patients with isolated COPD, regardless of the risk of developing the underlying disease, an increase in the level of platelet growth AA factor and TNFα was noted. The level of platelet growth AA factor and TNFα in patients with COPD, regardless of the risk of exacerbation, was correlated with the functional state of the lungs, clinical phenotype and severity of clinical manifestations of the disease. The value of platelet growth AA factor above 317 ng/ml in patients with COPD may be an early marker of endothelial dysfunction and a predictor of the development of hemostatic disorders and concomitant cardiovascular pathology.

THE SEVERITY OF VASCULAR INFLAMMATION AND ITS RELATIONSHIP WITH CLINICAL AND FUNCTIONAL FEATURES IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE WITHOUT CONCOMITANT CARDIOVASCULAR PATHOLOGY

The Russian Federation is one of the countries with a high prevalence of chronic obstructive pulmonary disease (COPD). In the last decade, the list of families of chemical regulators of vascular inflammation in COPD has been supplemented with information about growth factors, whose participation in the processes of regulation of vascular function seems significant. The study of the role of angiogenesis factors in patients with isolated COPD disease is insufficient at this stage and needs to be clarified. Objective. To study was to identify diagnostic and prognostic criteria for the severity of vascular inflammation and to assess its relationship with clinical and functional features in patients with COPD without concomitant cardiovascular pathology in comparison with the clinical phenotype of the disease. Material and methods. 96 patients with COPD were examined, the median age was 61 years. In addition to standard clinical, functional and laboratory research methods, the severity of vascular inflammation was assessed in all examined patients with the determination of quantitative indicators of human platelet growth AA factor and tumor necrosis factor-α (TNFα) by quantitative solid-phase enzyme immunoassay Results. In all patients with isolated COPD, regardless of the risk of developing the underlying disease, an increase in the level of platelet growth AA factor and TNFα was noted. The level of platelet growth AA factor and TNFα in patients with COPD, regardless of the risk of exacerbation, was correlated with the functional state of the lungs, clinical phenotype and severity of clinical manifestations of the disease. The value of platelet growth AA factor above 317 ng/ml in patients with COPD may be an early marker of endothelial dysfunction and a predictor of the development of hemostatic disorders and concomitant cardiovascular pathology.

Endothelial dysfunction in patients with obesity and type 2 diabetes mellitus or normoglycemia: assessment of specific markers

BACKGROUND: One of the function of the endothelium is the maintenance of body's homeostasis. Endothelial dysfunction is known to be profoundly implicated in the pathogenesis of cardiovascular diseases (CVD). The presence of diabetes mellitus significantly increases the risks of CVD. Type 2 diabetes mellitus (T2DM) is often observed in obesity, however, there is a population of people with obesity, who do not develop T2DM for a long time.AIM: To compare the level of markers of endothelial dysfunction in two groups of individuals (without T2DM and with T2DM), as well as to evaluate the impact of cardioprotective medication (GPP-1 and SGLT-2) on these markers.MATERIALS AND METHODS: We recruited 2 groups of patients with obesity into this study: the 1st group with no carbohydrate metabolism disorders, the 2nd with T2DM. Several markers of endothelial dysfunction were evaluated: human von Willebrand factor (VWF), vascular endothelial growth factor A (VEGF-A), soluble form E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM1).RESULTS: A significant increase in sE-Selectin was seen in the group of patients with obesity and T2DM compared with those without carbohydrate metabolism disorders (46.65 [36.23; 66.66] vs 33.05 [22.1;53.31] ng/ml). There were no differences in the level of markers of endothelial dysfunction in the subgroups of patients with T2DM with HbA1c < 8% and >8%. There was also no effect of cardioprotective drugs (SGLT-2 and / or GPP-1) on any of endothelial dysfunction markers in individuals with T2DM.CONCLUSION: We suggest that an increase in sE-selectin may be an early marker of endothelial dysfunction in obese individuals and T2DM.

Correlation of Mid-Trimester Spot Urinary Albumin: Creatinine Ratio With the Adverse Pregnancy Outcome.

Background Urinary albumin creatinine ratio (ACR) is a known method of measurement of microalbuminuria. Microalbuminuria may be an early marker of endothelial dysfunction which can lead to various complications during the course of pregnancy. The objective of our study was to evaluate the correlation of mid-trimester spot urinary ACR with the pregnancy outcome. Material and methods We performed a prospective cohort study in the department of Obstetrics & Gynaecology,All India Institute of Medical Sciences, Bhopal, for a period of one year. We studied 130 antenatal women between 14 and 28 weeks of gestation after obtaining written informed consent. The patients with ongoing urinary tract infection (UTI), pre-existing hypertension, or diabetes were excluded. Urinary samples were examined for spot ACR, and the women were followed untildelivery. Primary maternal outcomes were development of gestational hypertension, pre-eclampsia, gestational diabetes mellitus (GDM), and preterm labour. Neonatal outcome was assessed in terms of birth weight, the APGAR (Appearance, Pulse, Grimace, Activity, Respiration) scores, and neonatal intensive care unit (NICU) admission. Results In our study, mean urinary ACR was 19.07±12.94 mcg/mg and median urinary ACR (IQR) was 18 (9.43-25.25) mcg/mg. Prevalence of microalbuminuria in our study was 19.2%. It was observed that urinary ACR level was significantly higher in women with maternal complications like GDM, gestational hypertension, preeclampsia, and preterm labour. Also, mean urinary ACR of women who developed preeclampsia was higher (37.53±31.85)compared to women who developed gestational hypertension (27.40±9.71). Urinary ACR level was significantly higher in babies with low APGAR scores and in babies who needed NICU admission (p value < 0.05). The sensitivity and specificity of spot urinary ACR to predict GDM and preeclampsia were found to be good as calculated from the receiver operating curve. Conclusion We found definite correlation of higher values of mid-trimester urinary ACR with the adverse pregnancy outcome.

Assessment of Surrogate Markers for Cardiovascular Disease in Familial Mediterranean Fever-Related Amyloidosis Patients Homozygous for M694V Mutation in MEFV Gene.

Cardiovascular disease (CVD) remains underestimated in familial Mediterranean fever-associated AA amyloidosis (FMF-AA). We aimed to compare early markers of endothelial dysfunction and atherosclerosis in FMF-AA with a homozygous M694V mutation (Group 1 = 76 patients) in the Mediterranean fever (MEFV) gene and in patients with other genotypes (Group 2 = 93 patients). Measures of increased risk for future CVD events and endothelial dysfunction, including flow-mediated dilatation (FMD), pentraxin-3 (PTX3), and carotid intima-media thickness (cIMT), and fibroblast growth factor 23 (FGF23) as a marker of atherosclerotic vascular disease were compared between groups. The frequency of clinical FMF manifestations did not differ between the two groups apart from arthritis (76.3% in Group 1 and 59.1% in Group 2, p < 0.05). FMD was significantly lower in Group 1 when compared with Group 2 (MD [95% CI]: −0.6 [(−0.89)–(−0.31)]). cIMT, FGF23, and PTX3 levels were higher in Group 1 (cIMT MD [95% CI]: 0.12 [0.08–0.16]; FGF23 MD [95% CI]: 12.8 [5.9–19.6]; PTX3 MD [95% CI]: 13.3 [8.9–17.5]). In patients with FMF-AA, M694V homozygosity is associated with lower FMD values and higher cIMT, FGF23, and PTX3 levels, suggesting increased CVD risk profiles. These data suggest that a genotype–phenotype association exists in terms of endothelial dysfunction and atherosclerosis in patients with FMF-AA.

ZMPSTE24 Regulates SARS-CoV-2 Spike Protein-enhanced Expression of Endothelial PAI-1.

Endothelial dysfunction is implicated in the thrombotic events reported in patients with coronavirus disease (COVID-19), but the underlying molecular mechanisms are unknown. Circulating levels of the coagulation cascade activator PAI-1 are substantially higher in patients with COVID-19 with severe respiratory dysfunction than in patients with bacterial sepsis and acute respiratory distress syndrome. Indeed, the elevation of PAI-1 is recognized as an early marker of endothelial dysfunction. Here, we report that the rSARS-CoV-2-S1 (recombinant severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] viral envelope spike) glycoprotein stimulated robust production of PAI-1 by human pulmonary microvascular endothelial cells (HPMECs). We examined the role of protein degradation in this SARS-CoV-2-S1 induction of PAI-1 and found that the proteasomal degradation inhibitor bortezomib inhibited SARS-CoV-2-S1–mediated changes in PAI-1. Our data further show that bortezomib upregulated KLF2, a shear-stress–regulated transcription factor that suppresses PAI-1 expression. Aging and metabolic disorders are known to increase mortality and morbidity in patients with COVID-19. We therefore examined the role of ZMPSTE24 (zinc metallopeptidase STE24), a metalloprotease with a demonstrated role in host defense against RNA viruses that is decreased in older individuals and in metabolic syndrome, in the induction of PAI-1 in HPMECs by SARS-CoV-2-S1. Indeed, overexpression of ZMPSTE24 blunted enhancement of PAI-1 production in spike protein–exposed HPMECs. In addition, we found that membrane expression of the SARS-CoV-2 entry receptor ACE2 was reduced by ZMPSTE24-mediated cleavage and shedding of the ACE2 ectodomain, leading to accumulation of ACE2 decoy fragments that may bind SARS-CoV-2. These data indicate that decreases in ZMPSTE24 with age and comorbidities may increase vulnerability to vascular endothelial injury by SARS-CoV-2 viruses and that enhanced production of endothelial PAI-1 might play role in prothrombotic events in patients with COVID-19.

The association of low-grade albuminuria with incident non-alcoholic fatty liver disease and non-invasive markers of liver fibrosis by glycaemia status.

Low-grade albuminuria, as an early marker of endothelial dysfunction and kidney damage, has been recognized as a risk factor for metabolic disorders. Epidemiological studies manifesting the association of low-grade albuminuria with the risk of incident NAFLD and fibrosis were not available. We aimed to investigate the association of low-grade albuminuria with incident NAFLD and fibrosis by glycaemia status. A prospective population-based study was performed in 3308 participants without NAFLD at recruitment. Baseline urinary albumin excretion was obtained by a first-voided early morning spot urine sample. At follow-up visit, incident NAFLD was diagnosed by hepatic ultrasound after excluding alcohol abuse and other cause of hepatic diseases. Fatty liver index (FLI) was employed to reflect liver fat content. Liver fibrosis was evaluated by NAFLD fibrosis score (NFS), fibrosis-4 score (FIB-4) and Hepamet fibrosis score (HFS) respectively. After 4.3years of follow-up, 622 (18.8%) were detected as incident NAFLD. Participants with low-grade albuminuria imposed a 40.4% [1.404 (1.112-1.772)] greater risk on incident NAFLD, and 52.0% [1.520 (1.141-2.026)], 87.4% [1.874 (1.291-2.720)] and 40.4% [1.404 (1.038-1.898)] higher risks on newly onset higher values of FLI, NFS and FIB-4 respectively. The effect of low-grade albuminuria was stronger in the subgroup of non-diabetic population. Low-grade albuminuria was independently associated with incident NAFLD and a higher probability of fibrosis, especially among non-diabetic individuals.

Evaluation of serum endocan levels in relation to epicardial fat tissue thickness in metabolic syndrome patients.

IntroductionMetabolic syndrome has been recognized as a predictor of cardiovascular diseases. Epicardial fat tissue (EFT) thickness has recently been shown to be a predictor of cardiovascular diseases in metabolic syndrome patients. Endocan is a novel molecule which is considered to be an early marker of endothelial dysfunction. Our aim was to evaluate endocan serum levels for the first time in metabolic syndrome patients, in relation to EFT thickness.Material and methodsThe study included 44 patients with metabolic syndrome who had neither chronic kidney disease nor chronic inflammation and 26 healthy controls. Fasting blood samples were obtained from the groups. The serum levels of endocan were measured with a Sunred ELISA kit. EFT thickness of patients was measured by echocardiography.ResultsThe serum endocan levels were significantly lower in the metabolic syndrome patients compared to the healthy controls (120.71 ±90.17 pg/ml vs. 414.59 ±277.57, p < 0.001). Metabolic syndrome patients demonstrated significantly higher EFT (p = 0.042). EFT thickness had a positive correlation with age (r = 0.397, p = 0.008) and weight (r = 0.010). However, there was no correlation with serum endocan (r = –0.021, p = 0.893) or other parameters. Regression analysis revealed that waist circumference is the parameter among metabolic syndrome criteria having the strongest relationship with serum endocan levels (β = –0.499, p = 0.21).ConclusionsEFT thickness was high in metabolic syndrome patients and can be a useful marker for cardiovascular risk assessment. However, serum endocan levels were found to be low and there was no correlation with EFT thickness. Large sample sized prospective studies are needed to clarify the relation of endocan levels with the other clinical indicators of cardiovascular risk in metabolic syndrome.

Effects of sunitinib on endothelial dysfunction, metabolic changes, and cardiovascular risk indices in renal cell carcinoma.

BackgroundSunitinib is a standard treatment for metastatic renal cell carcinoma (RCC). Currently, the data available on the effects of sunitinib on endothelial dysfunction, metabolic changes, and cardiovascular (CV) risk factors are limited, and we aimed to evaluate these aspects in patients with RCC after a short period of treatment.MethodsPatients affected by metastatic RCC were enrolled and evaluated before starting sunitinib (T0) and after 40 days of treatment (T1) by the flow‐mediated dilation (FMD), carotid intima media thickness (IMT), ankle‐brachial pressure index (ABI), and 24‐hour proteinuria. We also assessed serum metabolic and nutritional parameters at T0 and T1.ResultsTwenty patients (7 female), with a mean age of 61.4 ± 12.0 years, were studied. Overtime, we observed a reduction in estimated glomerular filtration rate (P = .002), FMD (P = .001) and in fasting plasma glucose levels (P = .04), as well as an increase in plasma insulin (P < .001), HOMA‐IR (P < .01), and serum total cholesterol levels (P = .01). Moreover at T1 we found a significant increase in systolic and diastolic blood pressure (P ≤ .001) and 24‐hour proteinuria (P < .001) compared to baseline, whereas no changes in IMT and ABI were detected.ConclusionThe changes observed overtime after sunitinib treatment in terms of markers of early endothelial dysfunction, blood pressure, as well as in glucose/insulin metabolism and proteinuria may contribute to increase CV risk in RCC patients and suggest a strict follow‐up in this setting. Larger evidences are mandatory to confirm our observations.

Endothelial Microparticle as an early Marker of Endothelial Dysfunction in Patients with Essential Hypertension: A Pilot Study.

Hypertension is a global health burden causing immense morbidity and mortality especially from the complications of end-organ damage. It is expected to affect 29% of the population by the year 2025. Hypertension is usually asymptomatic; it is diagnosed by a disease of exclusion. Numerous factors such as inflammation, oxidative stress, genetic predisposition etc. play roles in the pathogenesis of hypertension. Endothelial microparticles (EMPs) are released into the circulation with the onset of changes in endothelium, even before the release of other routine vascular endothelial markers. EMPs mediate inflammation, thrombosis and vasoconstriction of blood vessels in hypertensives. This pilot study was undertaken to assess whether EMPs are early markers of endothelial dysfunction in essential hypertensive patients. The study was conducted as a large case control study in which 525 individuals were involved. It consisted of three study groups: Group I: individuals with normal blood pressure (JNC8), group II: hypertensives without evidence of end-organ damage and group III: hypertensives with evidence of end-organ damage. Homocysteine, hsCRP, fibrinogen, eNOS, oxLDL and other markers were measured. For analysis of EMPs a subset of individuals are taken from each group. Control group of 10 individuals who had homocysteine level more than15μmol/L was taken as Group I. Another 10 individuals were taken randomly of five each from groups II and III. EMPs were analyzed by flow cytometry and were identified as CD31 +, CD42 - microparticles with diameters < 1.0mm. There was significant increase in EMPs (p = 0.035) in hypertensive individuals with end organ damage. Measurement of EMPs in hypertensive individuals could help physicians in identifying and initiating therapeutic interventions at a very early stage of the disease, thus improving the quality of life.

P5456The role of ST2 as an early marker of endothelial dysfunction in hypertensive patients

Abstract Background The association between endotelial dysfunction and progression of diastolic dysfunction suggests that endotelial and myocardial impairment might have similar pathogenic pathways. Moreover, in hypertensive diabetics the endotelial function is worse in those with impaired diastolic performance compared to normal diastolic performance. ST2 provides additional data to echocardiography in early detection of diastolic performance alteration in hypertension (HT) and is a prominent predictive marker of worse clinical outcome in hypertensive patients. There is scarce data on ST2 role in detection of early vascular involvement in hypertensive patients. Purpose The aim of the study is to evaluate whether ST2 levels correlate with impaired endotelial function in hypertensive patients. Methods Our prospective study included 84 hypertensive patients (mean age 52.9±14.4 yrs, 54.3% males and 45.7% females), after they signed an informed consent. All patients underwent clinical and laboratory (including ST2) evaluation. To investigate endothelial function, we performed ultrasound measurement of the brachial artery diameter both at rest and during reactive hyperemia in the muscle distal to the brachial artery (BA) which causes endothelium-dependent vasodilatation. The study methodology was approved by the Ethical Committee and statistical data processing was performed with SPSS. Results Patients were assigned to group A – those without left ventricular hypertrophy (LVH) and group B – those with LVH. There were no significant differences regarding gender, age and HT stage between groups A and B. Patients in group A had lower ST2 levels [18.83 (13.98 - 42.05) vs 55.63 (48.6 - 100.21) vs, p&lt;0.001] and fewer risk factors (1.4 vs 2.6, p&lt;0.01) compared to group B. We found significant differences regarding diastolic performance parameters between the groups. The relative increase in diameter (% FMD; DD = D 100) was significantly higher in group A than group B (6.67±0.43% vs 3.10±0.33%, p&lt;0.01). ST2 levels were greater in group B and correlated with the degree of endotelial dysfunction evaluated by flow-mediated dilatation (FMD) (r=0.411, p&lt;0.01). Multiple regression analysis showed that ST2 had a significant negative correlation with the relative increase in arterial diameter while multivariate Cox regression analysis showed ST2 was an independent predictor of endothelial dysfunction severity in hypertensive patients (hazard ratio: 4.012, 95% confidence interval: 1.207–31.24, P=0.031). Conclusions ST2 levels correlate with cardiovascular risk and are a significant predictive marker of endothelial dysfunction in hypertensive patients regardless of diastolic dysfunction.

Endothelium-dependent and cyclooxygenase-dependent cutaneous vasodilatation is blunted in young men with hypertensive parents

Across ethnicities, offspring of hypertensive parents (OH) have higher risk of hypertension than offspring of normotensive parents (ON). Sympathetic hyperactivity and reduced nitric oxide availability have been reported in normotensive OH; but the role of vasodilator cyclooxygenase (COX) products is unclear. In 12 OH and 12 ON men (19-24 years old), each group comprising six white Europeans and six South Asians with resting ABP less than 129/89 mmHg, reactive hyperaemia and responses evoked by iontophoresis pulses of acetylcholine (ACh) were recorded in forearm skin by laser Doppler fluximetry before and after COX inhibition. Peak reactive hyperaemia was larger in ON than OH (71.0 ± 7.8 vs. 43.4 ± 8.3 perfusion units (perf.units); P < 0.05). It was attenuated by COX inhibition in ON (24.8 ± 5.2 perf.units, P < 0.01), not OH (54.2 ± 7.5 perf.units). Similarly, increases in perfusion evoked by ACh were greater in ON than OH (169.1 ± 20.4 vs. 142.1 ± 19.9 perf.units; P < 0.05) and attenuated by COX inhibition in ON (94.5 ± 13.7; P < 0.05), not OH (132.6 ± 16.1 perf.units). Considering ethnicities, ACh-evoked dilation, though not reactive hyperaemia was greater in Europeans than Asians (176.8 ± 21.7 vs. 130.4 ± 15.0; P < 0.01; 61.0 ± 8.7 vs. 51.7 ± 9.2 perf.units). However, within both Europeans and Asians, COX inhibition attenuated reactive hyperaemia and ACh-induced dilatation in ON only. Reactive hyperaemia and ACh-evoked dilatation in cutaneous circulation are blunted in young, normotensive OH relative to ON men irrespective of white European, or South Asian ethnicity and are attributable to impaired contribution of COX vasodilator products in OH. These features may provide early markers of endothelial dysfunction that contribute to hypertensive risk in OH men.

Clinical features of endothelial dysfunctions in patients with obesity and role of smoking

Introduction and purpose. The article presents data on the obesity and endothelial dysfunction, on influence of smoking on the developing of endothelial dysfunction. Material and methods. Examined 108 patients (90 women and 18 men) with obesity aged 45 to 65 years old (middle age 54.62±0.43) with different degrees of obesity. Vasomotor endothelial function was evaluated by the method of Celermajer et al. Analyzed early markers of endothelial dysfunction in patients with metabolic syndrome. Statistical processing of the data using a nonparametric Wilcoxon-Konovalov and Mann-Whitney. Conclusions. Based on the study preliminary conclusions can be made of the importance of identifying early markers of endothelial dysfunction in these patients and how smoking influences on developing of vascular pathology in patients with obesity.

Endocan Serum Levels in Patients with Non-Alcoholic Fatty Liver Disease with or without Type 2 Diabetes Mellitus: A Pilot Study.

Non-alcoholic fatty liver disease (NAFLD) is emerging as an independent cardiovascular risk factor. Recently, Endocan has been studied as an early marker of endothelial dysfunction. Our aim was to evaluate Endocan serum levels in patients with NAFLD with or without type 2 diabetes mellitus. We enrolled 56 patients: 19 with NAFLD and 37 with type 2 diabetes mellitus with or without NAFLD, and compared them to 25 healthy controls. Endocan serum level was measured by using the ELISA EndoMark assay. Endocan level was significantly higher in NAFLD subjects, compared to controls (1.23+/-1.51 vs 0.68+/-0.4 ng/mL; p=0.016). It was higher in patients with non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH) (1.12+/-1.11, 1.49+/-2.16 and 0.68+/-0.4 ng/ml vs controls, respectively), independently from presence of type 2 diabetes mellitus. The increase was more marked in patients with NASH and in those with NAFL versus controls (p=0.001 and p=0.004, respectively), but not statistically different between the two groups (p=0.448). Finally, we found a statistically relevant increase of this marker in diabetic NAFLD patients compared to those non diabetic (1.56+/-0.81 vs 0.72+/-0.58 ng/ml; p=0.01). We demonstrated an increased Endocan serum level in NAFLD patients, higher in those with type 2 diabetes mellitus and/or NASH because of an endothelial dysfunction in these pathologies.

Impact of high serum Immunoglobulin E levels on the risk of atherosclerosis in humans.

BackgroundEpidemiological studies show that immunoglobulin E (IgE) levels were higher in subjects with acute coronary events. However, it is unknown if the increased IgE level is a marker of future coronary incidents and whether it may be regarded as a risk factor of an ischemic heart disease.ObjectiveOur aim was to investigate the relationship between IgE levels and some atherosclerotic markers in patients without known atherosclerotic disease.MethodsFifty patients (mean age, 40.96 ± 10.8 years) with high serum IgE levels due to various conditions who did not display evidence of an atherosclerotic disease and 30 healthy control subjects (mean age, 47 ± 8.27 years) were included in the study. Atherosclerotic disease markers including adhesion molecules like vascular cell adhesion molecule-1, intercellular adhesion molecule-1, proinflammatory cytokines such as interleukin-6, endothelin-1, and systemic inflammatory markers such as high sensitivity C-reactive protein were determined by enzyme-linked immunosorbent assay (ELISA). Endothelial functions of the coronary arteries were determined by coronary flow reserve (CFR) measurements and carotid intima media thickness using transthoracic Doppler echocardiography.ResultsCFR was significantly lower in the patient group when compared with the control group (p<0.001; 95% confidence interval, -0.79 to-0.20) while carotid media thicknesses were not different between 2 groups. There were no differences in ELISA test results between the 2 groups.ConclusionOur results showed that CFR as an early marker of endothelial dysfunction was significantly lower in patients with high IgE levels. This finding seems to support the role of IgE in the vascular pathology of atherosclerosis.

SERUM OMENTIN-1 LEVELS AND ENDOTHELIAL DYSFUNCTION IN OBESITY.

Our aim was to investigate the relationship between serum omentin-1 levels and endothelial dysfunction in obese patients. We evaluated 50 obese patients, and age/gender matched 45 healthy non-obese subjects as controls. Oral glucose tolerance test, lipid parameters, uric acid levels, homeostatic model assessment-insulin resistance (HOMA-IR) index, serum omentin-1 levels and flow mediated dilatation (FMD) % were measured in all subjects. Body compositions were analyzed with bioelectrical impedance method using a Tanita Body Composition Analyzer and ViScan. Serum omentin-1 levels were found significantly lower in obese population compared to the control subjects. FMD response was significantly decreased in obese population. There was a significant positive correlation between serum omentin-1 levels and FMD response (r=0.359, p<0.001). Serum omentin-1 levels were negatively correlated with body mass index (BMI), waist circumference, total fat percentage, visceral fat, fasting insulin and HOMA-IR index. Lower serum omentin-1 levels and decreased FMD response may be an early marker of endothelial dysfunction in obese patients.

Osteopontin is BMI-independently Related to Early Endothelial Dysfunction in Children.

Osteopontin (OPN) has been proposed to predict adverse cardiac events in patients with adult type 2 diabetes. We investigated potential associations of circulating OPN and OPN expression in adipose tissue (AT) with obesity and early metabolic and cardiovascular dysfunction in children. Furthermore, we assessed the functional relevance of OPN on primary human endothelial cells. Serum OPN was determined in healthy lean (n = 65) and obese (n = 100) children by ELISA. Expression levels were assessed in sc AT samples from healthy lean (n = 33) and overweight and obese (n = 31) children by qRT-PCR. Direct effects of recombinant (rh) OPN on adhesion molecule and ENOS expression were assessed in human coronary arterial endothelial cells. OPN serum concentrations decreased with pubertal development in lean children. The degree of obesity was negatively associated with OPN serum levels. Multiple regression analysis revealed that body mass index (BMI) standard deviation score (SDS), next to pubertal status, was the strongest independent predictor for OPN serum concentrations. Metabolically, the homeostasis model assessment index and circulating plasma insulin were negatively correlated with OPN serum levels secondary to obesity. In contrast, independent from BMI, OPN was positively related to VCAM-1 levels, intima media thickening, and negatively associated with endothelial function. Functionally, full-length rhOPN did not affect adhesion molecule and ENOS mRNA expression in primary human coronary arterial endothelial cells. In addition, OPN expression levels in AT positively correlated with BMI SDS, AT inflammation, and markers of metabolic dysfunction but were not related to OPN serum levels. Our findings suggest that OPN levels are BMI-independently related to markers of early endothelial dysfunction in children.

ALBUMINURIA AS A MARKER OF ENDOTHELIAL DYSFUNCTION AND EARLY PREDICTOR OF CARDIOVASCULAR COMPLICATION IN PATIENTS WITH DIABETES MELLITUS

The necessity to identify was grounded and assesses the dynamics of albuminuria and glomerular filtration rate in patients with type 1 and type 2 diabetes (as an early marker of endothelial dysfunction and a predictor of cardiovascular complication) on the background of pathogenetic therapy with glycosaminoglycans sulodexide was done. Clinically significant reduction in the excretion of both total protein and albumin in the urine was found. It indicates an improvement of microcirculation in the kidney along with an increase in glomerular filtration rate. The increase in the glomerular filtration rate is most pronounced in patients with type 2 diabetes with comorbid non-alcoholic fatty liver disease.

Comparison in young White European (WE) and South Asian (SA) men of endothelium‐dependent cutaneous vasodilator responses: contribution of cyclooxygenase (COX) products

It is established that cardiovascular disease is more prevalent in South Asians (SA) than White Europeans (WE). The prevalence of diabetes central obesity and metabolic syndrome is particularly high in SAs, disorders that are associated with endothelial dysfunction. It is not known whether early markers of endothelial dysfunction can be detected even in young healthy SAs. Thus, we have compared responses evoked in recreationally‐active WE and SA men (18–25 years; n=10 in each case). SAs were 1st or 2nd generation residents in the UK with mother and father originating from India, Sri Lanka, Bangladesh or Pakistan; WEs were UK residents with WE parents. By using laser Doppler fluximetry, we monitored changes in cutaneous red cell flux (RCF) evoked in the cutaneous circulation of the forearm by iontophoresis of the endothelium‐dependent dilator acetylcholine (ACh, 8 × 20s pulses: 7 at 100 μA, 8th at 200 μA, at 60s intervals) and by release of arterial occlusion for 3 min (reactive hyperaemia). Responses were tested before and after aspirin (600mg p.o.) to assess the role of COX products. Mean arterial blood pressure (ABP) was continuously monitored by photoplethysmography using a finger cuff. Resting ABP was similar in WEs and SAs (124±1.8/70±1.7 vs 116.6±2.0/65.4±1.6 mmHg) and did not change during the protocol. Baseline RCF was also similar in WEs and SAs: 19.7±1.9 vs 12.3±0.9 perfusion units (PU), respectively. Further, ACh evoked similar dilator responses in WEs and SA, maximum RCF reaching 192.2±5.5 and 182.83 ± 5.20 perfusion units (PU) respectively. Aspirin had no net effect on ACh‐induced dilatation in either group (WEs: 182.6±4.5 and SAs: 193.0± 7.7 PU) indicating any influence of COX dilator and vasoconstrictor products was balanced in both WEs and SAs. By contrast, before aspirin, reactive hyperaemia was substantially larger in WEs than SA, peak RCF being 92.9±2.5 vs 74.2±3.1*PU, *: P&lt;0.01 RMANOVA). Further, aspirin attenuated reactive hyperaemia in WEs, peak RCF being only 75.1 ± 2.6§PU: §: P&lt;0.001 vs control response, but enhanced reactive hyperaemia in SAs, peak RCF reaching 84.7±2.7§PU. These results suggest that in young SA men, who have no overt signs of cardiovascular disease and are normotensive, there are already signs of endothelial dysfunction. Agonist‐evoked endothelium‐dependent dilatation is apparently normal in SAs with no net contribution from COX dilator or vasoconstrictor products, suggesting that nitric oxide and/or Endothelium‐dependent hyperpolarising factor are the main contributors in both ethnicities. However, reactive hyperaemia, which is induced by the combination of shear‐stress and metabolic stimuli, is blunted in young SAs relative to WEs and this is attributable to a predominating influence of vasoconstrictor COX products in SAs, but vasodilator COX products in WEs.Support or Funding InformationAlexander S. Onassis Public Benefit Foundation

Additive Effect of Non-Alcoholic Fatty Liver Disease on Metabolic Syndrome-Related Endothelial Dysfunction in Hypertensive Patients.

Metabolic syndrome (MS) is characterized by an increased risk of incident diabetes and cardiovascular (CV) events, identifying insulin resistance (IR) and endothelial dysfunction as key elements. Moreover, non-alcoholic fatty liver disease (NAFLD) is bidirectionally linked with MS as a consequence of metabolic and inflammatory abnormalities. We addressed the question if the evolution in NAFLD might worsen endothelium-dependent vasodilating response in MS hypertensives. We recruited 272 Caucasian newly-diagnosed never-treated hypertensive outpatients divided into three groups according to the presence/absence of MS alone or in combination with NAFLD. MS and NAFLD were defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and non-invasive fatty liver index, respectively. We determined IR by using the homeostasis model assessment (HOMA) index. Vascular function, as forearm blood flow (FBF), was determined through strain-gauge plethysmography after intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside. MS+NAFLD+ group showed worse metabolic, inflammatory and vascular profiles compared with MS−NAFLD− and MS+NAFLD−. HOMA resulted in being the strongest predictor of FBF both in the MS+NAFLD− and in the MS+NAFLD+ groups, accounting for 20.5% and 33.2% of its variation, respectively. In conclusion, we demonstrated that MS+NAFLD+ hypertensives show a worse endothelium-dependent vasodilation compared with MS+NAFLD−, allowing for consideration of NAFLD as an early marker of endothelial dysfunction in hypertensives.