Early Predictor Of Atherosclerosis Research Articles

Evaluation of antibodies to oxidized low-density lipoprotein in children with obesity of different degrees

Introduction. The interest in the study of anti-oxidized low-density lipoproteins (anti-oxLDL) is due to their association with the development and progression of atherosclerosis and metabolic syndrome. Purpose of the study. To study the level of antibodies of oxidized low-density lipoproteins (anti-oxLDL) in serum in obese children. Materials and Methods. 76 children aged 5 to 17 years participated in the study. A standard objective and laboratory examination was performed, including physical and sexual development, lipidogram and anti-oxLDL levels. To assess anthropometric data, the standard deviation coefficient was calculated using the Auxology application. The parameters of fat metabolism were determined according to the data of blood biochemical analysis. The content of anti-oxLDL was determined by immuno-enzymatic analysis using test kits “Biomedica”. Results. According to the results of the examination the patients were divided into three groups: group 1 included 36 children with constitutional-exogenous obesity and increased level of anti-oxLDL, group 2-30 patients with constitutional-exogenous obesity and normal level of anti-oxLDL, group 3-10 healthy children. The level of antibodies to oxidized low density lipoproteins (oxLDL) in obese children is 11.6 times higher compared to healthy children. The antibody titer in prepubertal children is 2206 [1809;2603] IU/mL, and in adolescents it is 1505.5 [1109;1902] IU/mL. The highest values of anti-oxLDL levels were observed in patients with 1st degree obesity 2623 [2245;3001] IU/mL and 3rd degree obesity 2914.5 [2678;3151] IU/mL. Conclusion. High of anti-oxLDL levels were found in pre-pubertal children with obesity, especially in 1st and 3rd degree obesity. In obese children, the level of anti-oxLDL has a direct correlation with the duration of the underlying disease and the increase in low-density lipoprotein (LDL) levels. Further studies are needed on the role of anti-OCOLDL as an early predictor of atherosclerosis in clidren with obesity.

Variability of flow-mediated dilation across lower and upper limb conduit arteries

Endothelial dysfunction is an early predictor of atherosclerosis and cardiovascular disease. Flow-mediated dilation (FMD) is the gold standard to assess endothelial function in humans. FMD reproducibility has been mainly assessed in the brachial artery (BA) with limited research in lower limb arteries. The purpose of this study was to compare FMD reproducibility in the upper limb BA and lower limb superficial femoral artery (SFA) in young healthy adults.Fifteen young healthy adults (nine males; six females) underwent FMD, resting diameter, velocity, and shear rate measurements on three occasions to determine intra-and inter-day reproducibility in both BA and SFA, assessed by coefficient of variation (CV), intraclass correlation coefficient (ICC), and Bland–Altman plots.BA FMD CVs (intra-day: 4.2%; inter-day: 8.7%) and ICCs (intra-day: 0.967; inter-day: 0.903) indicated excellent reproducibility and reliability, while for SFA FMD, both CVs (intra-day: 11.6%; inter-day: 26.7%) and ICCs (intra-day: 0.898; inter-day: 0.651) showed good/moderate reproducibility and reliability. BA FMD was significantly more reproducible than SFA FMD (p < 0.05). Diameter reproducibility was excellent and similar between arteries, while resting velocity and shear rate have lower reproducibility in the BA compared to SFA. Bland–Altman plots displayed no proportional and fixed bias between measurements.In summary, SFA FMD is less reproducible than BA FMD, with identical volume of ultrasound training. Given the increasing interest in using SFA FMD to test the efficacy of interventions targeting lower limb’s vascular health and as a potential biomarker for peripheral arterial disease risk, future studies should ensure higher levels of training for adequate reproducibility.

Improving impact of heparan sulfate on the endothelial glycocalyx abnormalities in atherosclerosis as revealed by glycan-protein interactome

Endothelial dysfunction induced by oxidative stress is an early predictor of atherosclerosis, which can cause various cardiovascular diseases. The glycocalyx layer on the endothelial cell surface acts as a barrier to maintain endothelial biological function, and it can be impaired by oxidative stress. However, the mechanism of glycocalyx damage during the development of atherosclerosis remains largely unclear. Herein, we established a novel strategy to address these issues from the glycomic perspective that has long been neglected. Using countercharged fluorescence protein staining and quantitative mass spectrometry, we found that heparan sulfate, a major component of the glycocalyx, was structurally altered by oxidative stress. Comparative proteomics and protein microarray analysis revealed several new heparan sulfate-binding proteins, among which alpha-2-Heremans-Schmid glycoprotein (AHSG) was identified as a critical protein. The molecular mechanism of AHSG with heparin was characterized through several methods. A heparan analog could relieve atherosclerosis by protecting heparan sulfate from degradation during oxidative stress and by reducing the accumulation of AHSG at lesion sites. In the present study, the molecular mechanism of anti-atherosclerotic effect of heparin through interaction with AHSG was revealed. These findings provide new insights into understanding of glycocalyx damage in atherosclerosis and lead to the development of corresponding therapeutics.

SUMOylation and coupling of eNOS mediated by PIAS1 contribute to maintenance of vascular homeostasis.

Endothelial dysfunction (ED) is commonly considered a crucial initiating step in the pathogenesis of numerous cardiovascular diseases. The coupling of endothelial nitric oxide synthase (eNOS) is important in maintaining normal endothelial functions. However, it still remains elusive whether and how eNOS SUMOylation affects the eNOS coupling. In the study, we investigate the roles and possible action mechanisms of protein inhibitor of activated STAT 1 (PIAS1) in ED. Human umbilical vein endothelial cells (HUVECs) treated with palmitate acid (PA) invitro and ApoE-/- mice fed with high-fat diet (HFD) invivo were constructed as the ED models. Our invivo data show that PIAS1 alleviates the dysfunction of vascular endothelium by increasing nitric oxide (NO) level, reducing malondialdehyde (MDA) level, and activating the phosphatidylinositol 3-kinase-protein kinase B-endothelial nitric oxide synthase (PI3K-AKT-eNOS) signaling in ApoE-/- mice. Our invitro data also show that PIAS1 can SUMOylate eNOS under endogenous conditions; moreover, it antagonizes the eNOS uncoupling induced by PA. The findings demonstrate that PIAS1 alleviates the dysfunction of vascular endothelium by promoting the SUMOylation and inhibiting the uncoupling of eNOS, suggesting that PIAS1 would become an early predictor of atherosclerosis and a new potential target of the hyperlipidemia-related cardiovascular diseases.

Endothelial dysfunction as predictor of atherosclerosis during a translatitudinal sea voyage in the Arctic: prospective study

INTRODUCTION. Human labor activity in the Arctic takes place in severe climatic conditions associated with cooling, atmospheric pressure drops, high humidity, photoperiodicity, low oxygen content in the air. Endothelial dysfunction is an early pathophysiological sign and an independent predictor of poor prognosis in most cardiovascular diseases.&#x0D; OBJECTIVE.Тo analyze the dynamics of the level of metalloproteinase-9 and thrombin activity as predictors of the development of atherosclerosis in sailors during a translatitudinal sea voyage in the Arctic.&#x0D; MATERIALS AND METHODS. A prospective clinical and laboratory study of crew members was performed during the integrated marine research expedition “Transarctic-2019”. A clinical and laboratory study of the level of metalloprotease-9 (enzyme-linked immunosorbent assay), coagulation analysis of the parameters of the thrombin generation test, as well as ultrasonic dopplerography of the thickness of the intima-media complex were carried out. Statistical data processing was carried out using the methods of descriptive and analytical statistics in the StataCorp Stata 14.2 program. The study protocol was approved by the local ethical committee of the SSMU (protocol No. 03/5 dated May 27, 2015) and supported by the state task reg. No. NIOKTR 121030300111-7.&#x0D; RESULTS. A statistically significant increase in the level of MMP-9 in sailors after the expedition was noted, the relationship between the level of MMP-9, indicators of the thrombin generation test (lag time, min (p=0.0190), tPeak (p=0.0177), Peak (p= 0.0217) and KIM thickening.&#x0D; DISCUSSION. MMP-9 levels may be a predictor of early atherosclerosis and atherosclerotic plaque instability, as well as a risk factor for future adverse cardiovascular events. The relationship of MMP-9 with the kinetics of thrombin (one of the regulators of the antithrombotic state of the endothelium) during a translatitudinal voyage in sailors indicates the formation of readiness for prothrombotic events.&#x0D; CONCLUSION. Thus, in Arctic conditions, under conditions of chronic oxidative stress, which contribute to the progression of the development of endothelial dysfunction in the presence of external risk factors, the likelihood of progression of atherosclerotic vascular lesions increases, and, as a result, the development of vascular events.

Osteopontin as an early predictor of atherosclerosis in attack-free Familial Mediterranean fever patients.

Familial Mediterranean fever (FMF) is an autoinflammatory disease that is associated with endothelial dysfunction and atherosclerosis. Osteopontin which is a multifunctional protein involved in the modulation of inflammatory processes may contribute to the development of atherosclerosis in FMF patients. Therefore, this cross-sectional study investigated the relationship of osteopontin with carotid intima media thickness (CIMT) and atherogenic indices in patients with FMF. Serum osteopontin levels, CIMT, Castelli risk index I and II, plasma atherogenic index (PAI), non - high-density lipoprotein cholesterol, and atherogenic coefficient (AC) in 64 attack-free FMF patients were compared with levels in 23 healthy control subjects. The serum osteopontin level, CIMT, Castelli risk index I, AC and PAI were significantly higher, and high-density lipoprotein cholesterol was significantly lower in FMF patients (P < .001, P < .001, P = .045, P = .016, P = .045, and P = .024; respectively). There were significant positive correlations between osteopontin and CIMT, PAI, AC, and Castelli risk index I (R = 0.580, R = 0.259, R = 0.233, R = 0.277; respectively) and there was significant negative correlation between osteopontin and high-density lipoprotein cholesterol (r= -0.309). Patients who had homozygote mutations had significantly higher osteopontin, PAI, Castelli risk index I and II level. The current study is the first to demonstrate significantly increased serum osteopontin levels in attack-free FMF patients compared with healthy controls. It was also associated with CIMT and many atherogenic indices. This finding provides a new experimental basis to understand the pathogenesis of inflammation-induced atherosclerosis in FMF patients. Furthermore, patients who had homozygote mutations had worse atherogenic indices than those with heterozygote mutations.

Assesmen of atherosclerotic lesions of the carotid artery and risk factors for rheumatoi arthritis patients

Aim . To study and evaluate risk factors and analyze carotid artery intima-media thickness parameters as an early predictor of atherosclerosis in patients with rheumatoid arthritis. Materials and methods . The study involved 86 patients (women - 67, men - 19) observed in the State Institution “City Medical Center №2”, Dushanbe, aged from 37 to 67 years (mean age - 56.5±2.9 years). The diagnosis of rheumatoid arthritis was established according to the American College of Rheumatologists/EULAR 2010 criteria. The examination program included general clinical and instrumental methods (examination of common and accessible parts of internal and external carotid arteries), estimation of lumen size, the thickness of intima-media complex (TCIM), straightness of its course, atherosclerotic plaques of carotid arteries (ABS), echocardiography (ECHO-KG). Results and discussion . Thus, in the absence of significant gender differences in the frequency of arterial hypertension and increased intima-media thickness (the earliest manifestation of atherosclerotic vascular lesions), hypercholesterolemia and long-term glucocorticoid intake were more frequently recorded in women. Undoubtedly, each of the considered risk factors makes a definite contribution to the development of vascular atherosclerosis and the instability of their organic changes. However, the significance of these risk factors in the thickening of the intima-media complex of vessels may differ. Conclusion . Data correlated with intima-media thickness show sex differences, the significance of risk factors, and an increase in intima-media thickness despite the duration of glucocorticoid therapy. The factors mentioned are more significant in men, while in women, intima-media thickness is closely related to the duration of rheumatoid arthritis, total cholesterol levels, and blood pressure.

Novel predictors of early atherosclerosis in nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is regarded as the most relevant liver disease of the twenty-first century, affecting at least one third of the general population. NAFLD is associated with increased mortality due to cardiovascular disease (CVD) and cancer. The carotid intimal media thickness (CIMT), mean platelet volume (MPV) and endocan level could be markers for generalised atherosclerotic burden and endothelial dysfunction. The aims of the study were to evaluate the association between non-alcoholic fatty liver disease and early atherosclerosis by measuring CIMT, MPV and endocan level, as markers of endothelial dysfunction, in NAFLD patients. This cross-sectional study included 50 patients who were divided into two groups: group I included 25 subjects with NAFLD and group II included 25 healthy subjects. Complete blood count with MPV, liver profile, lipid profile, fasting blood glucose level, 2-hour postprandial kidney function test, and serum concentrations of endocan were measured for all patients. NAFLD fibrosis score (NFS) was calculated. Abdominal ultrasonography and carotid ultrasound scan for measurement of CIMT were performed. Serum endocan levels, MPV and CIMT were significantly higher (p < 0.005) in NAFLD patients (0.6, 9.3 ±1.2 and 0.9 ±0.3 respectively) than healthy subjects (0.1, 8.1 ±0.6 and 0.6 ±0.1 respectively). The analysis of diagnostic performance of these factors revealed that they have good sensitivity and specificity in prediction of endothelial dysfunction with AUC (0.950, 0.844 and 0.849 respectively). Serum endocan levels, MPV and CIMT could be considered as good predictors of endothelial dysfunction and therefore early detection of subclinical atherosclerosis in NAFLD patients.

The vascular response to acute hyperglycaemia: What is the role of exercise capacity?

The vascular response to acute hyperglycaemia: What is the role of exercise capacity?

Age and Interleukin-15 Levels Are Independently Associated With Intima-Media Thickness in Obesity-Related NAFLD Patients.

Common carotid intima-media thickness (IMT) represents a functional and structural marker of early, precocious, and subclinical atherosclerosis, independently from the carotid plaque. Macrophage cells, which have been detected in adipose tissue and atherosclerotic plaques, are regulated by interleukin-15 (IL-15). At the light of the conflicting results concerning the role of IL-15 in atherosclerosis, the aim of the study was to retrospectively evaluate in a population of 80 obese patients, with median age of 46 years (IQR 34–53 years), with a low rate of comorbidities but with non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis (HS), the relationship between IMT and serum concentrations of IL-15. Anthropometric measures, metabolic profile, and serum inflammatory markers, as well as the levels of IL-15, MCP-1, b FGF, and GM-CSF, were analyzed by a bead-based assay. IMT, HS, subcutaneous, and visceral adipose tissues were detected by ultrasonography. The IL-15 levels of the obese patients were increased with respect to those of 44 young healthy subjects, i.e., 2.77 (1.21–4.8) vs. 1.55 (1–2.4) pg/mL (P = 0.002). In the univariate analysis, IL-15 levels were associated to IMT and to those of MCP-1, b FGF, and GM-CSF, without any relation to other inflammatory markers such as CRP and ferritin, except fibrinogen. In the multivariate analysis, after adjusting the HS severity for the extent of visceral adiposity, a dramatic change in prediction of IMT by HS was shown (β from 0.29 to 0.10, P from 0.008 to 0.37). When the visceral adipose tissue was combined with IL-15, on the one hand, and the well-known coronary artery disease (CAD) risk factors—i.e., age, gender, smoking status, HDL-cholesterol concentrations, triglycerides levels, and HOMA—on the other, only age and IL-15 remained the predictors of IMT (β = 0.60, P = 0.0001 and β = 0.25, P = 0.024, respectively). There was no association of IL-15 with various anthropometric parameters nor with body fat distribution and severity of HS, also after adjusting for age. Age is resulted to be the main factor in the prediction of IMT and thus of early atherosclerosis. The prediction of IMT by IL-15 coupled with the lack of prediction by the well-known CAD risks is in agreement with recent data, which emphasizes the main role of the immune system in the onset/worsening of atherosclerosis, even though the role of visceral adiposity should be further deepened. Age and IL-15 levels were both predictors of early atherosclerosis in this population of obese patients with NAFLD, suggesting a possible role of this cytokine in the atherosclerosis process.

Endothelial dysfunction as early predictor of atherosclerosis

Cardiovascular diseases in Russia are leading in the structure of total mortality. Atherosclerosis is considered a progressive inflammatory systemic disease. The role of endothelium in the development of the atherosclerotic process is described in detail. The main functions of endotheliocytes are normal and in various pathological conditions. The main markers of endothelial dysfunction are presented. Data on the development of the atherosclerotic process in time, risk factors are presented. Local and systemic risk factors for atherosclerosis are highlighted. Own data on the frequency of occurrence of atherosclerotic changes in the main vessels of the head in young people (up to 45 years) based on the results of ultrasonic duplex scanning during professional examinations are presented. The main directions of correction of endothelial dysfunction are described.

Serum Apelin: A New Marker of Early Atherosclerosis in Children with Type 1 Diabetes Mellitus.

INTRODUCTION:Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in children that may be complicated by micro or macrovascular complications. Measurement of the carotid intima-media thickness (CIMT) allows the early detection of atherosclerotic alterations of blood vessels that may complicate T1DM.SUBJECTS AND METHODS:This study is a case-control study. Participants were classified into two groups. The first group included 40 children with T1DM and the second group included 30 matched healthy controls. The studied cases were recruited from Endocrinology and Diabetology Unit, Pediatric Hospital, Ain Shams University. Serum apelin, cholesterol, TG, LDL were measured for every case. Also, albumin level was analyzed in urine. Measurement of the carotid intima-media thickness (CIMT) was done for all cases.RESULTS:Comparison between T1DM patients and controls revealed that serum apelin, cholesterol, TG, LDL and albuminuria were significantly increased in cases compared to controls. Significant positive correlations were detected between HbA1C, albuminuria and lipid profile with apelin in the diabetic group (p < 0.05). CIMT has significant positive correlation with serum apelin levels (r = 0.36, p = 0.05). Also, this study found positive correlations between CIMT and some variables as LDL, SBP z-score and duration of the illness.CONCLUSION:Increased levels of serum apelin in T1DM patients may be considered as predicting factor for the ongoing development of vascular sequels. This study highlighted the possible validity of apelin assay as an early predictor of atherosclerosis in T1DM children. Evaluating CIMT in these patients is of at most important for early detection of subclinical atherosclerosis.

Endothelial function in rheumatoid arthritis.

Rheumatoid arthritis (RA) patients are at higher risk of accelerated atherosclerosis. To assess endothelial dysfunction in RA to find a possible mechanistic pathway that will explain the clinical phenomenon. A prospective study recruited 44 RA patients with an active long standing (>12 months) disease. All underwent a detailed assessment of disease activity. To estimate the endothelial function the brachial artery method was performed, measuring flow mediated diameter percent (FMD%) change. Clustering analyses (hierarchical and k-means) were performed. Patients were compared to healthy subjects. Forty four RA patients (54.42 ± 11.14 years, females (72.7%)) with co-morbidities (70.5%), not taking tumor necrosis factor-blockers or disease modifying anti rheumatic drugs (63.6%). Only 6 (13.6%) had a normal endothelial function. Hierarchical and k-means clustering techniques showed statistically significant differences among the three clusters concerning disease activity score-28 (DAS-28)- erythrocyte sedimentation rate (ESR) (P = 0.000), DAS-28- C-reactive protein (CRP; P = 0.001), clinical disease activity index (P = 0.002), simplified disease activity index (P = 0.001), ESR (P = 0.000), (CRP) (P = 0.003) and FMD% (P = 0.009). The group with the highest FMD% values exhibited the lowest clinical scores and laboratory parameters. Patients with the lowest FMD% values co-clustered with subjects with positive but low FMD% changes and elevated clinical and laboratory parameters. Our study confirmed the feasibility of exploiting endothelial function in clinical practice as an early predictor of atherosclerosis in RA patients.

Intima media thickness as an early predictor of atherosclerosis in Egyptian children with familial Mediterranean fever.

IntroductionFamilial Mediterranean fever (FMF) is an autosomal recessive disease. It is characterized by recurrent crises of fever and serosal inflammation. Although FMF patients are symptom free in between attacks, subclinical inflammation continues during the attack-free period. Such patients with inflammatory status have an increased risk of atherosclerotic cardiovascular complications. We attempted to elucidate the role of arterial wall thickening as a predictor of early atherosclerosis in children affected by FMF and to clarify the links between carotid intima media thickness and the markers of subclinical inflammation serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), neutrophil-to-lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR).Material and methodsIt is a case control study. The study comprised 45 Egyptian children diagnosed with FMF and 45 healthy children of matched age and sex who served as controls, without family history or clinical manifestations suggestive of FMF. Laboratory investigations included complete blood count, NLR, PLR, ESR, C-reactive protein and lipid profile. Serum amyloid A levels were determined in both groups using enzyme linked immunosorbent assay. Assessment of the common carotid artery intima media thickness (CIMT) in the FMF patients was carried out.ResultsThe level of SAA was significantly higher in patients than the control subjects with a mean value of 38.30 ng/ml and 23.43 ng/ml respectively (p < 0.001). Our patients showed significantly higher PLR when compared to controls (p < 0.001). The mean right and left carotid intima media thickness in patient and control groups showed a highly significant difference (p = 0.005 and 0.036 respectively).ConclusionsThe mean carotid intima media thickness is higher in cases than the control group. Hence carotid intima media thickness may be used as a tool in the prediction of any atherosclerotic burden in those children.

Premature atherosclerosis in children with beta-thalassemia major: New diagnostic marker

BackgroundEarly vascular alteration, atherosclerosis and coronary artery disease have emerged as important cardiovascular complications among beta-thalassemia major (B-TM) patients. The aims of the current study were to assess the prevalence of premature atherosclerosis among our B-TM patients, and to investigate the diagnostic value of serum Osteoprotegerin assay as an early biomarker for atherosclerosis.MethodsThis cross-sectional study was conducted at Hematology unit - Pediatric Department, Zagazig University Children Hospital- Egypt in the period from March 2014 to March 2015. A total of 115 children were enrolled in the current study; as sixty-five (65) children with beta thalassemia major aged 5–18 years, on regular blood transfusion regimen represented the patient group. While fifty (50) healthy children, with comparable age and gender, were assigned as control group. All participants were subjected to history taking, thorough clinical examination and laboratory investigations including; complete blood count, liver and kidney function tests, C- reactive protein, lipid profile, serum ferritin and serum Osteoprotegerin (OPG) assay. Also, carotid artery intima media thickness (CAIMT) was performed by duplex ultrasound for patients and controls.ResultsOur B-TM patients were transfusion-dependent for as long as 8.5 ± 3.8 years with significantly higher serum ferritin levels (2490 ± 1579 ng/dl vs 83 ± 32 ng/dl, p = 0.001), C-reactive protein (5.7 ± 5.7 vs 0.9 ± 0.9), liver enzymes and bilirubin when compared to controls. Significantly higher serum triglyceride (128 ± 20 vs 101 ± 7 mg/dL, p = 0.009) and atherogenic index of plasma (0.45 ± 0.12 vs 0.22 ± 0.04, p = 0.001) were recorded in patients than comparisons. On the contrary, total serum cholesterol (116 ± 16 vs 143 ± 5, p < 0.001), low density lipoprotein-cholesterol (LDL-C) (44 ± 9 vs 73 ± 6, p < 0.001) and high density lipoprotein cholesterol (HDL-C) (39 ± 2 vs 61 ± 5, p < 0.001), were significantly lowered in patients versus normal peers. Carotid arteries intima media thickness (CAIMT) of both side were significantly increased for patients (Rt 0.62 ± 0.2 vs. 0.29 ± 0.07 mm, p = 0.001 & Lt 0.66 ± 0.17 vs 0.29 ± 0.05 mm, p = 0.001) when compared with healthy controls, and showed positive correlation with, serum triglyceride, atherogenic index of plasma, and serum Osteoprotegerin levels. ELISA assay of serum Osteoprotegerin (OPG) revealed significantly higher levels for thalassemia patients than matched healthy controls (427 ± 102 vs. 324 ± 126 pg/ml, p = 0.02). Of particular interest is the obvious positive correlation between OPG levels and CAIMT of both sides (Rt r 0.54, p = 0.001 &Lt r 0.479, p = 0.001) and also with serum triglycerides (r 0.374, p = 0.03).ConclusionsSubclinical atherosclerosis started prematurely in children with beta- thalassemia. Carotid artery intima media thickness represented a simple, accurate and non-invasivemodality for early detection ofatherosclerosis. It was correlated well with serum Osteoprotegerin; this finding highlighted the possible validity of OPG assay as an early predictor of atherosclerosis in thalassemia children.

Endothelial function in patients with rheumatologic diseases

Background. Сardiovascular diseases and their complications occupy one of the leading positions among causes of death in patients with rheumatologic diseases (RD), though the precise underlying mechanisms explaining fast progression of cardiovascular diseases are unknown. Early onset and high progression rate of atherosclerosis are the most common features, which cannot be fully explained by traditional cardiovascular risk factors. Inflammation, which is present in all RD and is involved in the pathogenesis of atherosclerosis, may contribute to the development of cardiovascular complications. Evaluation of the association between inflammation and endothelial dysfunction (an early predictor of atherosclerosis) may facilitate the understanding this mechanism. The objective of our study was to assess endothelial function in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), ankylosing spondylitis (AS) and rheumatoid arthritis (RA) and to evaluate the significance of various markers of endothelial dysfunction (ED), depending on the type of RD. Design and methods. The study enrolled 213 patients with various RD, 63 patients with ≥ 2 cardiovascular risk factors without RD and 10 healthy volunteers. Markers of endothelial dysfunction — homocysteine, asymmetric dimethylarginine (ADMA), endothelin 1–21, vascular cell adhesion molecule 1, 1sVCAM-1; intercellular adhesion molecule 1, sICAM-1 — and reactive hyperemia index (EndoPat 2000, Itamar Medical) were assessed in all patients. Results. The profile of ED markers differs in various RD, however, the most universal indicator is the ADMA level, especially in autoimmune RD with circulating autoantibodies (SLE, RA, SSc).

Eicosapentaenoic Acid Prevents Saturated Fatty Acid-Induced Vascular Endothelial Dysfunction: Involvement of Long-Chain Acyl-CoA Synthetase.

Vascular endothelial dysfunction is considered an early predictor of atherosclerosis. It has been proven that elevated blood levels of free fatty acids pose a substantial risk for the development of cardiovascular disease. In this study, we examined the effects of palmitic acid (PA), a saturated fatty acid, on endothelial function by using the expression of adhesion molecule, cytokines, and inflammatory protein as indicators, as well as investigated the effects of eicosapentaenoic acid, an n-3 polyunsaturated fatty acid. Human umbilical vein endothelial cells (HUVEC) were exposed to PA and EPA. When HUVEC were exposed to PA, there was an increase in the expression of adhesion molecule, cytokines, and inflammatory protein (ICAM-1, MCP-1, interleukin-6, PTX3). PA augmented the expression of long-chain acyl-CoA synthetase (ACSL) and the cyclin-dependent kinase inhibitor p21, and enhanced the phosphorylation of p65, a component of NF-κB. ACSL inhibition and siRNA-mediated ACSL3 knockdown suppressed the PA-induced increase in the expression of adhesion molecule, cytokines, and inflammatory protein, and ACSL inhibition suppressed the enhancement of p65 phosphorylation. In addition, p21 knockdown suppressed the PA-induced increase in the expression of MCP-1 and ICAM-1. EPA suppressed the PA-induced increase in the expression of ACSL and p21, the enhancement of p65 phosphorylation, as well as the associated increase in the expression of ICAM-1, MCP-1, interleukin-6, and PTX3. These results suggest that the ACSL, p21, and NF-κB-dependent pathway may possibly be involved in PA-induced vascular endothelial dysfunction, and that EPA ameliorates this at least in part through the regulation of ACSL3 expression.

Markers of early atherosclerosis, oxidative stress and inflammation in patients with acromegaly.

Data regarding atherosclerosis in acromegaly is controversial in literature. We aimed to investigate the markers of early atherosclerosis, oxidative stress, inflammation and their relationships with each other in acromegaly. Thirty-nine patients with acromegaly and 40 control subjects were enrolled. Patients were classified into two groups; active acromegaly (AA) and controlled acromegaly (CA). Controls were matched by age, gender, body mass index and presence of cardiovascular risk factors. Flow mediated dilatation (FMD), carotid intima media thickness (CIMT), epicardial adipose tissue thickness (EAT) were measured and serum levels of oxidative stress parameters, high mobility group box 1 protein (HMGB1) and high sensitive CRP (hs CRP) were evaluated. Significantly decreased FMD, increased CIMT and EAT were found in patients with acromegaly compared to controls (p<0.01, p<0.05, p<0.001, respectively). EAT correlated negatively with FMD (r=-0.24, p=0.038) and positively with CIMT (r=0.37, p<0.01). Presence of acromegaly, hypertension and age were found to be the predictors of early atherosclerosis (p<0.05). Hs CRP was decreased in AA compared to controls (p=0.01). There were no significant differences for HMGB1 and oxidized LDL (ox-LDL) cholesterol levels and total antioxidant capacity (TAC) between AA, CA and controls (p>0.05). Early atherosclerosis measured with FMD, CIMT and EAT may exist in acromegaly. However, decreased hs CRP and unchanged HMGB1, ox-LDL and TAC levels suggest that inflammation and oxidative stress do not seem to contribute to the development of atherosclerosis in these patients.

Statin Helps Endothelial Function in COPD Subgroup

Statin Helps Endothelial Function in COPD Subgroup

THU0547 Association of Asymptomatic Hyperuricemia and Endothelial Dysfunction in Psoriatic Arthritis

BackgroundCardiovascular disease is an increasingly recognized contributor to excess morbidity and mortality in psoriatic arthritis (PsA). Atherosclerosis is a multifocal, immune-inflammatory disease affecting the medium and large arteries. There is...