Markers Of Endothelial Dysfunction Research Articles

Evaluation of Serum Visfatin as a Biomarker of Lupus Nephritis in Egyptian Patients with Systemic Lupus Erythematosus.

One of the most significant consequences of systemic lupus erythematosus (SLE) is lupus nephritis (LN). Visfatin, an adipokine that is significantly expressed in visceral fat and is a marker of endothelial dysfunction in chronic kidney disease, has multiple proinflammatory actions. We aimed to evaluate the state of serum visfatin in SLE patients and to detect its possible correlation with the disease's activity and effects on the kidney affection. Fifty patients with active LN, 50 patients with inactive lupus, and 50 healthy people had their serum visfatin levels tested. Chemical and immunological markers of SLE and LN were measured. The SLE Disease Activity Index (SLEDAI) was used to measure the disease's activity. Renal biopsies from the LN subgroup were collected and classified using the modified classification of the World Health Organization. The serum visfatin of patients with active LN was significantly greater than that of inactive lupus patients and the healthy controls (20.56 ± 1.07 ng/mL, 16.77 ± 1.02 ng/mL, and 9.96 ± 1.46 ng/mL, P <0.001). SLEDAI and serum visfatin levels were shown to be significantly correlated (P = 0.000057). Serum visfatin levels were likewise significantly correlated with the index of histological activity in the active group (P <0.00001). Serum visfatin was raised in individuals with active LN and was related to the SLEDAI and disease severity scores. Serum visfatin could be utilized as a noninvasive biomarker for evaluating the severity of LN and risk stratification of the risk.

Endocan as a Potential Marker for Predicting All-Cause Mortality in Hemodialysis Patients

Endocan, a pro-inflammatory cytokine and pro-angiogenic factor, is a marker of endothelial dysfunction and has been proven to correlate with cardiovascular disease. In hemodialysis (HD) patients, cardiovascular disease is the major cause of mortality. Our study aimed to investigate the relationship between serum endocan and all causes of mortality in HD patients. A total of 103 patients, aged over 20 years old and undergoing HD for more than 3 months, were included and followed for 36 months. Mortality events, serum endocan, biochemical data, body mass index, systolic and diastolic blood pressure, baseline characteristics, and the use of antihypertensive and lipid-lowering drugs were recorded. In our study, a total of 26 deaths (25.2%) occurred. Hemodialysis patients with diabetes mellitus, older age, higher serum endocan, and lower creatinine and albumin levels had a higher risk of mortality. Adjusting for prognostic variables, HD patients with higher serum endocan (p = 0.010) and lower serum creatinine (p = 0.034) demonstrated significantly higher all-cause mortality. In our study, increased endocan and lower creatinine are associated with all-cause mortality in HD patients. Serum endocan levels could serve as a biomarker for a high mortality risk in HD patients.

Peroxisome proliferator-activated receptor gamma and osteoprotegerin levels as an indicator and diagnostic predictor of endothelial dysfunction

Abstract Objectives Peroxisome proliferator-activated receptor gamma (PPAR-γ) modifies many cellular processes that contribute to atherosclerosis. The increased concentrations of osteoprotegerin (OPG) are related with coronary artery disease, calcification in vascular tissue, advanced atherosclerosis, and diabetic complications has been informed. The aim of our study was to define the relation among PPAR-γ Pro12Ala and, OPG and PPAR-γ in Peripheral Vascular Disease (PVD) and hypertension (HT). Also, it was aim to investigate the relationship between flow-mediated dilatation (FMD) in HT and ankle brachial index (ABI) in PVD in terms of endothelial dysfunction (ED). Methods Fifty-four patients with HT, 47 with PVD, and 52 healthy for the controls were included. Blood samples were used for analyzing PPAR-γ and OPG by Enzyme-Linked Immunosorbent Assay (ELISA), and biochemical assays. The PPAR-γ Pro12Ala was examined using TaqMan with PrimerProbMix. p value less than 0.05 was accepted as the limit of significance. Results The PPAR-γ was significantly decreased in both HT and PVD (p&lt;0.001). The serum concentrations of OPG were higher in HT (p&lt;0.001) and increased in diabetic ones (p&lt;0.05). CG genotype of PPAR-γ Pro12Ala was more frequent in HT patients (p&lt;0.001). In the HT patients, increased OPG and decreased PPAR-γ were found in CC (p&lt;0.001). In the PVD patients, PPAR-γ levels decreased in carrying with CC (p&lt;0.05). Conclusions It may be significant that increased OPG, as a marker of endothelial dysfunction, is found in HT. Moreover, decreased PPAR-γ in those who have to carry CC may be protective in both HT and PVD.

Studying the effect of different combinations of neuroprotectors on biochemical markers of inflammation, endothelial dysfunction and apoptosis in patients with ischemic stroke

Background. Preservation and restoration of neurons in the ischemic penumbra by developing new methods for neuroprotection is one of the urgent issues of modern medicine. The purpose was to study the effect of different combinations of neuroprotectors with different mechanisms of action by analyzing markers of inflammation, endothelial dysfunction, and apoptosis in the blood serum of patients with ischemic stroke. Materials and methods. A randomized prospective controlled study was conducted on the use of neuroprotective complexes (NPC): NPC 1 (cerebrolysin + mexidol) and NPC 2 (cerebrolysin + citicoline), in patients with moderate and severe ische-mic stroke. They were randomly divided into groups: 1) comparison group — standard therapy; 2) NPC 1 along with standard treatment; 3) NPC 2 against the background of standard treatment. Laboratory studies on assessing interleukin-6, endothelin-1 and caspase-8 in blood serum were performed in dynamics, on days 1, 4 and 7. Results. In terms of anti-inflammatory activity, the therapy scheme, which included the administration of NPС 2, was 1.6–2.1 times (p &lt; 0.01) ahead of standard treatment, as well as 1.2–1.4 times (p &lt; 0.05) — of standard treatment combined with NPC 1. The regimen, which included NPC 2, in terms of endothelium protection and antiapoptotic effect exceeded standard treatment alone by 1.8–3.5 and 1.5–2.3 times (p &lt; 0.01), respectively, as well as by 1.2–1.5 and 1.2–1.3 times (p &lt; 0.05) — standard treatment combined with the use of NPС 1. Conclusions. The use of NPС 2 (cerebrolysin + citicoline) for the treatment of moderate and severe ischemic strokes in combination with standard therapy showed the most pronounced and reliable neuroprotective effect (p &lt; 0.05).

Endothelial dysfunction in postoperative purulent-septic complications of hepatobiliary zone pathologies

Objective. Determination of the significance of endothelial dysfunction in postoperative purulent-septic complications of pathologies of the hepatobiliary zone.Material and methods. An analysis was conducted on 57 patients who underwent surgery for pathologies of the hepatobiliary zone and subsequently developed postoperative purulent-septic complications. Among these, there were 17 cases of postoperative peritonitis, 20 cases of postoperative intra-abdominal abscesses, and 20 cases of postoperative pancreatic necrosis. Of the patients, 19 were men (33.3%), and 38 were women (66.7%). Their ages ranged from 20 to 71 years.Results. Out of the 57 patients, when classified based on the severity of endotoxemia: 26.3% had a mild degree, another 26.3% had a moderate degree, 15% had a severe degree, and 21.0% had an extremely severe degree. High levels of oxidative stress markers and decreased SOD levels were particularly evident in patients with postoperative intra-abdominal abscesses. Furthermore, even greater acceleration of lipid peroxidation processes was observed in patients with severe endotoxemia resulting from widespread postoperative peritonitis and extensive to nearly total postoperative pancreatic necrosis. Additionally, significant changes were noted in endotoxemia predictors in portal blood, endothelial dysfunction markers, and cytokines in patients with postoperative intra-abdominal purulent-septic complications.Conclusion. Endothelial dysfunction in patients with postoperative purulent-septic complications is associated with profound pathomorphological changes in hepatocytes. These changes are evident in alterations to rheology, microcirculation, and increased levels of endothelial dysfunction markers.

Prophylactic treatment can modify vascular risk biomarkers in high-frequency episodic and chronic migraine patients: a pilot study

To evaluate whether preventive treatment can modify endothelial and oxidative biomarkers of vascular disease risk in patients with high-frequency episodic and chronic migraine. In this observational, prospective pilot study, 88 prophylactic treatment-naïve patients with episodic and chronic migraine and 56 healthy sex/age matched controls underwent ultrasonography exams and blood tests at baseline, and again in the migraine patients after 3 months’ treatment with metoprolol or topiramate. Biomarkers for endothelial function and oxidative stress were analyzed. At baseline, patients with migraine in the low-frequency episodic group had differences exclusively in nitrates 17.6 versus 27.33 µM; p = 0.046 compared to the controls. However, when comparing the group comprised of patients with high-frequency episodic migraine and chronic migraine versus controls, statistically significant differences appeared in hsCRP 2.68 versus 1.64 mg/dL; p = 0.049, vWF antigen (133% vs. 110%; p = 0.020, vWF activity (111% vs. 90%; p = 0.010) and isoprostane levels (181 vs. 238 µM; p = 0.05). Only in the chronic migraine subgroup did we found statistically significant differences in CIMT (0.60 vs. 0.54 mm; p = 0.042) which were significantly greater than in the controls. After treatment, patients who respond to preventive treatment exhibited significantly higher levels of nitrates (24.2–13.8 µM; p = 0.022) and nitrites (10.4–3.43 µM; p = 0.002) compared than non-responders. Moreover, biomarker levels improved in treatment-responsive patients with migraine; hsCRP levels decreased from 2.54 to 1.69 mg/dL (p < 0.05), vWF activity levels decreased from 124 to 103 IU/dL (p = 0.003) and prothrombin activity decreased from 1.01 to 0.93 (p = 0.01). These differences were also observed in the high-frequency and chronic migraine subgroup and reach statistical significance in the case of hsCRP, which decreased from 2.12 to 0.83 mg/dL (p = 0.048). Patients with migraines have differences in biomarker levels compared to controls, suggesting endothelial and oxidative dysfunction. The greatest differences in biomarker levels compared to controls are observed in migraine patients in the high-frequency and chronic migraine subgroups. Based on our results, preventive treatment is capable of modifying markers of endothelial dysfunction and oxidative stress in migraine patients, even in cases of chronic and high-frequency migraine.

Albuminuria as a marker of atherosclerosis burden and a possible predictor of adverse events in patients with polyvascular disease

The role of albuminuria as a marker of the atherosclerosis burden and a predictor of prognosis in patients with polyvascular disease (PD) has been little studied. To evaluate the prevalence, association with atherosclerosis burden, and prognostic value of albuminuria in relation to cardiovascular and bleeding complications in patients with PD. The data was obtained from the prospective registry REGATA-1 (NCT04347200). Seventy four patients (75.7% males, median age 67 [61-69] years) with PD (CAD and peripheral arterial disease) were enrolled. All patients received aspirin and rivaroxaban 2.5 mg. The albumin-creatinine ratio in a single morning urine sample, estimated glomerular filtration rate (eGFR), and von Willebrand factor levels were determined. Mild albuminuria (10-29 mg/g) was detected in 45.9% of patients, moderate and severe (≥30 mg/g) - in 29.7%; eGFR<60 ml/min - in 21.7%, chronic kidney disease (CKD) according to the full KDIGO criteria (eGFR and/or albuminuria ≥30 mg/g) - twice as often (39.2%). The frequency of nephroprotective therapy prescription was insufficient. The level of albuminuria did not correlate with von Willebrand factor (endothelial dysfunction marker), but was associated with affecting of 4-5 vascular beds (ROC AUC 0.775; p=0.011). During the follow-up (12 [8-18] months) 3 patients developed MACE, 11 - BARC 2-3 bleedings. Neither albuminuria nor eGFR were predictors of MACE, bleeding, or net clinical benefit. CKD (KDIGO) was also not associated with bleedings. CKD (KDIGO) was independent predictor of MACE (in significant multiple regression model beta - coefficient for CKD was 0.097; p=0.042), however, the small number of end points allows us to speak only of a hypothesis-generating trend. The implementation of CKD (KDIGO) has increased the predictive value of the REACH score. Albuminuria is highly prevalent in patients with PD. It is a marker of atherosclerosis burden. CKD, diagnosed taking into account the level of albuminuria, can be used in a comprehensive assessment of cardiovascular risk in this category of patients.

Circulating levels of miR125a, miR126, and miR146a-5p in patients with obstructive sleep apnea and their relation with markers of endothelial dysfunction.

obstructive sleep apnea (OSA) is a prevalent sleep disorder that is associated with increased risk factors for cardiovascular diseases (CVDs). Oxidative stress, insulin resistance, inflammation, and endothelial dysfunction are increased in OSA patients and microRNAs (miRs) are regulatory elements that influence these pathological mechanisms. miR125a, miR126, and miR146a-5p play a role in these pathological mechanisms and have not been evaluated in patients with OSA. This case-control study was performed on 90 OSA patients and 34 controls. Circulating levels of miR125a, miR126, and miR146a-5 were determined using real-time PCR, and serum levels of hsCRP, ICAM-1, and VCAM-1 were evaluated using ELISA kits. miR125a and miR146a were elevated in patients with OSA compared to controls while miR126 decreased significantly. All three miRs indicated a remarkable difference between the mild-OSA group compared to the severe-OSA group. Furthermore, patients with OSA showed elevated levels of hsCRP, ICAM-1, and VCAM-1. Multiple linear regression indicated an independent association of miR125a with ICAM-1 and hsCRP, miR126 associated with VCAM-1 and total cholesterol, and miR146a-5p represented an association with apnea-hypopnea index and ICAM-1. Furthermore, miR146a-5p illustrated a good diagnostic ability to differentiate between OSA and controls. Circulating miR125a, miR126, and miR146a-5p fluctuations in patients with OSA and their relations with markers of endothelial dysfunction provide in vivo evidence and suggest a potential role for these miRs with endothelial dysfunction in patients with OSA.

Beneficial effects of recombinant CER-001 high-density lipoprotein infusion in sepsis: results from a bench to bedside translational research project.

Sepsis is characterized by a dysregulated immune response and metabolic alterations, including decreased high-density lipoprotein cholesterol (HDL-C) levels. HDL exhibits beneficial properties, such as lipopolysaccharides (LPS) scavenging, exerting anti-inflammatory effects and providing endothelial protection. We investigated the effects of CER-001, an engineered HDL-mimetic, in a swine model of LPS-induced acute kidney injury (AKI) and a Phase 2a clinical trial, aiming to better understand its molecular basis in systemic inflammation and renal function. We carried out a translational approach to study the effects of HDL administration on sepsis. Sterile systemic inflammation was induced in pigs by LPS infusion. Animals were randomized into LPS (n = 6), CER20 (single dose of CER-001 20mg/kg; n = 6), and CER20 × 2 (two doses of CER-001 20mg/kg; n = 6) groups. Survival rate, endothelial dysfunction biomarkers, pro-inflammatory mediators, LPS, and apolipoprotein A-I (ApoA-I) levels were assessed. Renal and liver histology and biochemistry were analyzed. Subsequently, we performed an open-label, randomized, dose-ranging (Phase 2a) study included 20 patients with sepsis due to intra-abdominal infection or urosepsis, randomized into Group A (conventional treatment, n = 5), Group B (CER-001 5mg/kg BID, n = 5), Group C (CER-001 10mg/kg BID, n = 5), and Group D (CER-001 20mg/kg BID, n = 5). Primary outcomes were safety and efficacy in preventing AKI onset and severity; secondary outcomes include changes in inflammatory and endothelial dysfunction markers. CER-001 increased median survival, reduced inflammatory mediators, complement activation, and endothelial dysfunction in endotoxemic pigs. It enhanced LPS elimination through the bile and preserved liver and renal parenchyma. In the clinical study, CER-001 was well-tolerated with no serious adverse events related to study treatment. Rapid ApoA-I normalization was associated with enhanced LPS removal and immunomodulation with improvement of clinical outcomes, independently of the type and gravity of the sepsis. CER-001-treated patients had reduced risk for the onset and progression to severe AKI (stage 2 or 3) and, in a subset of critically ill patients, a reduced need for organ support and shorter ICU length of stay. CER-001 shows promise as a therapeutic strategy for sepsis management, improving outcomes and mitigating inflammation and organ damage. The study was approved by the Agenzia Italiana del Farmaco (AIFA) and by the Local Ethic Committee (N° EUDRACT 2020-004202-60, Protocol CER-001- SEP_AKI_01) and was added to the EU Clinical Trials Register on January 13, 2021.

Effects of Probiotics and Fibers on Markers of Nephropathy and Endothelial Dysfunction in Persons with Type 1 Diabetes and Albuminuria

Effects of Probiotics and Fibers on Markers of Nephropathy and Endothelial Dysfunction in Persons with Type 1 Diabetes and Albuminuria

Elevated indoleamine 2,3-dioxygenase activity is associated with endothelial dysfunction in people living with HIV and ROS production in human aortic endothelial cells in vitro.

The precise role of indoleamine 2,3-dioxygenase (IDO) in cardiovascular diseases (CVD) among people living with HIV (PLWH) is still under debate, despite recognized links. This study aimed to investigate the impact of elevated IDO activity on endothelial dysfunction in PLWH. A total of 38 PLWH, who had not previously received anti-retroviral therapy (ART), were enrolled in the study. These participants were monitored for 36 months following the initiation of ART. Measurements including plasma levels of IDO activity, markers of endothelial dysfunction, inflammatory factors, and lipids. In vitro, human aortic endothelial cells (HAEC) were exposed to interferon-γ, an IDO inhibitor, a kynurenine 3-hydroxylase (KMO) inhibitor, as well as different concentrations of kynurenine. Pre-ART, PLWH demonstrated notably elevated plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1(sVCAM-1), and IDO activity in comparison to healthy controls. Post-ART, both IDO activity and sICAM-1 levels experienced a significant decrease, with IDO activity reaching levels comparable to those observed in healthy controls. Furthermore, a positive correlation was observed between IDO activity and sICAM-1 (p = 0.0002), as well as sVCAM-1 (p < 0.0001) before ART. In vitro, the augmentation of kynurenine concentration in the medium and the induction of IDO expression in HAEC resulted in increased production of reactive oxygen species (ROS), with minimal impact on endothelial dysfunction. From these findings, it can be concluded that long-term ART has the potential to restore the heightened IDO activity observed in PLWH. The overexpression of IDO primarily influences the expression of ROS in HAEC.

Изучение эффективности лечения эндотелиальной сосудистой дисфункции при различных стадиях первичной открытоугольной глаукомы

Relevance. According to literary sources, POAG is considered as a chain of interaction of etiological and pathogenetic factors, among which the leading role is played by genetic predisposition, general changes, ischemia, primary local functional and dystrophic changes, disturbances in hydrostatics and hydrodynamics of the eye, increased intraocular pressure, vascular disorders, dystrophy and tissue degeneration. Purpose of the study. To assess the severity of endothelial dysfunction in patients with different stages of primary open-angle glaucoma during complex therapy. Material and research methods. The study included 92 patients with POAG aged 65 to 80 years, who were divided into three groups. We studied the levels of endothelin-1, VEGF and von Willebrand factor before and after the recommended treatment in patients with POAG. Conclusion. The developed complex therapy of various stages in patients with POAG contributed to the correction of the identified disorders in relation to markers of endothelial dysfunction. The features of changes in ED markers in patients with POAG have been established; low levels of von Willebrand factor, VEGF and endothelin-1, which indicates the role of pathogenetic factors in the formation of endothelial dysfunction and the importance of studying markers of endothelial dysfunction. Keywords: primary open-angle glaucoma, endothelial markers, von Willebrand factor, VEGF, endothelin-1, complex therapy

Physical exercise in patients with testicular cancer treated with bleomycin, etoposide and cisplatin chemotherapy: pulmonary and vascular endothelial function—an exploratory analysis

PurposeBleomycin, etoposide, and cisplatin combination chemotherapy (BEP) improves the survival of patients with testicular cancer, but is associated with potentially life-threatening toxicities like pneumonitis and thromboembolic events. This study explored the effects of physical exercise in patients with testicular cancer during or after BEP-chemotherapy on pulmonary and vascular endothelial toxicity.MethodsIn this post hoc analysis of a multicenter randomized clinical trial (NCT01642680), patients with metastatic testicular cancer scheduled to receive BEP-chemotherapy were randomized to a 24-week exercise intervention, initiated during (group A) or after BEP-chemotherapy (group B). Endpoints were pulmonary function (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), lung transfer-coefficient and transfer factor for carbon monoxide (KCO, DLCO) and markers of vascular endothelial dysfunction (von Willebrand factor (vWF) and factor VIII).ResultsThirty patients were included. Post-chemotherapy, patients declined less in FVC, FEV1 and DLCO in group A compared to group B. Post-chemotherapy, vWF and factor VIII were significantly lower in group A compared to group B. After completion of exercise, started either during BEP-chemotherapy or thereafter, no between-group differences were found. At 1-year post-intervention, significant between-group differences were found in favour of group A in DLCO and KCO.ConclusionsPatients who exercised during BEP-chemotherapy better preserved FVC, FEV1 and DLCO, measured directly post-chemotherapy and 1-year post-intervention (DLCO, KCO). This coincided with less increase in vWF and factor VIII measured directly post-chemotherapy. These data support a beneficial role of a physical exercise intervention during BEP-chemotherapy on pulmonary and vascular damage in patients with testicular cancer.Trial registryOptimal Timing of Physical Activity in Cancer Treatment (ACT) Registry URL: https://clinicaltrials.gov/ct2/show/NCT01642680. Trial registration number: NCT01642680.

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 &lt; 8% and &gt;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.

A case-control study of early-stage radiological markers of endothelial dysfunction and cardiovascular findings in patients with osteogenesis imperfecta: genotype-phenotype correlations.

Osteogenesis imperfecta (OI) is a disease caused by defective collagen synthesis. Collagen type 1 is found in many structures in the cardiovascular system. Endothelial dysfunction, which develops prior to the emergence of structural and clinical signs of atherosclerosis, isbelieved to play a key role in atherogenesis. Endothelial dysfunction may be detected presymptomatically by non-invasive radiologic methods, such as flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT). These modalities may provide early indicators of endothelial dysfunction. This cross-sectional comparative study aimed to investigate early-stage radiological markers of endothelial dysfunction and cardiovascular diseases in OI patients and healthy controls and to investigate the correlation of findings with OI genotype. Thirty patients diagnosed with OI were paired with thirty healthy age- and gender-matched controls and echocardiogram findings were compared. None of the patients had known underlying cardiovascular disease. The mean age was 13.18±2.91 years. According to Sillence classification, 15 patients had type 1 OI, 10 had type III, and 5 had type IV. Mean CIMT in the OI group was higher in the control group (OI group: 0.42±0.06 vs. healthy controls: 0.34±0.04mm, p<0.01), and mean FMD percent was lower in the patient group (p<0.01). Left ventricular ejection fraction was 78.97±10.32 vs. 77.56±8.50 %, (OI group: 7.00±3.06 vs. healthy controls: 12.14±1.99, p=0.56), and fractional shortening was 42.68±11.94 vs. 40.23±7.99 %, (p=0.35), in OI patients and controls, respectively. Pediatric patients with OI without clinical signs of cardiovascular abnormality had significantly worse CIMT and FMD findings than healthy controls. However, no difference was determined when comparing left ventricular ejection fraction or fractional shortening. OI patients may need to be screened for cardiovascular system complications starting from an early age.

Metabolic syndrome, soluble CD40L, and biomarkers of endothelial dysfunction in people living with HIV.

In the present study, we aimed to investigate the association between soluble CD40 ligand (sCD40L, a marker of platelet activation), soluble thrombomodulin, and syndecan-1 (both well-described markers of endothelial dysfunction) and metabolic syndrome in a large cohort of well-treated people with HIV (PWH) and to elucidate their association with HIV-specific variables. We included 862 PWH with undetectable viral replication. Our hypotheses were tested using uni- and multivariable logistic regression models a priori adjusted for well-known confounders. While no association of soluble thrombomodulin and syndecan-1 with MetS was found, high levels of sCD40L (aOR 1.54 [1.07-2.22]) were associated with excess risk of MetS. Given the previously described association between sCD40L, vascular inflammation and endothelial damage, the results presented in our study may suggest a potential role for sCD40L in the well-known association between cardiometabolic comorbidity and HIV infection.

Blebbing of the plasma membrane of lymphocytes as a marker of endothelial dysfunction in the development of post-resection insufficiency in patients with focal liver lesions

Purpose of the study. To evaluate the intensity of blebbing of the plasma membrane of lymphocytes and the formation of microparticles of lymphocytic origin in patients with postresection hepatic failure. Material and methods. The study involved 54 patients with focal liver diseases. The study involved 32 (59%) women, 22 (41%) men. The average age was 59.5 [49.75; 66,00]. Patients were divided into groups, 1 group - 10 patients with developed acute liver failure and 2 group - 44 patients with a favorable course of postoperative period. The following surgical interventions were performed: 36 (67%) patients underwent surgery - laparotomy, segmental liver resection, 10 (18%) - left-sided hemihepatectomy and 8 (15%) - right-sided hemihepatectomy. Results. Predictors of early postoperative hepatic failure are a decrease in initial blebbing and an increase in terminal blebbing and free microparticles of lymphocytic origin. Conclusions. Thus, changes in lymphocyte blebbing and the presence of free microparticles of lymphocytic origin are due to the development of endothelial insufficiency and apoptosis of lymphocytes in the context of liver failure and are determined by the reduced function of residual liver volume.

Biomarkers of sustained systemic inflammation and microvascular dysfunction associated with post-COVID-19 condition symptoms at 24 months after SARS-CoV-2-infection.

Comprehensive studies investigating sustained hypercoagulability, endothelial function, and/or inflammation in relation to post-COVID-19 (PCC) symptoms with a prolonged follow-up are currently lacking. Therefore, the aim of this single-centre cohort study was to investigate serum biomarkers of coagulation activation, microvascular dysfunction, and inflammation in relation to persisting symptoms two years after acute COVID-19. Patients diagnosed with acute SARS-CoV-2 infection between February and June 2020 were recruited. Outcome measures included the CORona Follow-Up (CORFU) questionnaire, which is based on an internationally developed and partially validated basic questionnaire on persistent PCC symptoms. Additionally, plasma biomarkers reflecting coagulation activation, endothelial dysfunction and systemic inflammation were measured. 167 individuals were approached of which 148 (89%) completed the CORFU questionnaire. At 24 months after acute infection, fatigue was the most prevalent PCC symptom (84.5%). Over 50% of the patients experienced symptoms related to breathing, cognition, sleep or mobility; 30.3% still experienced at least one severe or extreme (4 or 5 on a 5-point scale) PCC symptom. Multiple correlations were found between several PCC symptoms and markers of endothelial dysfunction (endothelin-1 and von Willebrand factor) and systemic inflammation (Interleukin-1 Receptor antagonist). No positive correlations were found between PCC symptoms and coagulation complexes. In conclusion, this study shows that at 24 months after acute COVID-19 infection patients experience a high prevalence of PCC symptoms which correlate with inflammatory cytokine IL-1Ra and markers of endothelial dysfunction, especially endothelin-1. Our data may provide a rationale for the selection of treatment strategies for further clinical studies. This study was performed in collaboration with the CORona Follow-Up (CORFU) study (NCT05240742, https://clinicaltrials.gov/ct2/show/ NCT05240742).

SAT042 Impact Of Aerobic Exercise On The Circulating Endothelial Progenitor Cells And Inflammation Markers In Type 1 Diabetes

Abstract Disclosure: C.K. Maraschin: None. P.M. Bock: None. R.B. Monteiro: None. A. Alegretti: None. P.L. Lopes: None. L.P. Santos: None. L. Helal: None. R. Moraes: None. D.U. de Moraes: None. B.D. Schaan: None. The circulating levels of endothelial progenitor cells (EPCs) is a marker of endothelial dysfunction in many chronic diseases, including diabetes mellitus. Increasing the amount of circulating EPCs through exercise may be a viable strategy for improving endothelial function. However, differences in EPC levels between individuals with and without diabetes and the responses of EPCs to exercise sessions were not previously studied. We sought to determine the number of circulating EPCs by flow cytometry in subjects with or without type 1 diabetes (T1DM), and to elucidate the independent or combined responses of EPC populations and inflammatory markers in response to one bout of intense aerobic exercise. This was a non-randomized controlled trial. Fifteen adult males, ages 18–65, with T1DM were included. Patients with high glycemia in the morning of the study or with chronic diabetic complications that made it difficult to perform the protocol were excluded. Fifteen healthy, non-obese, non-smoking individuals were recruited as controls. All included subjects underwent an aerobic exercise session on a cycle ergometer for 30 minutes at 60% of the predetermined peak heart rate. Blood samples were collected to evaluate plasma glucose levels, glycated hemoglobin (HbA1c), total and HDL cholesterol, tumor necrosis factor alpha (TNFa), interleukin 6 (IL-6), and EPCs (CD45dim/CD34+/KDR+) before and after the exercise session. Individuals with T1DM presented higher fasting plasma glucose (197.3 ± 90.0 mg/dL vs. 88 ± 11.2 mg/dL, p &amp;lt; 0.01) and HbA1c levels (7.9 ± 1.5 vs. 5.0 ± 0.3%, p &amp;lt; 0.01), while peak VO2 was higher in controls (37.6 ± 8.4 vs. 29.1 ± 10.9 mL.kg-1.min-1, p = 0.03). A complete blood count analysis showed increases in white blood cells [0.8 (0.1, 1.4) and 1.0 (0.4, 1.6) x103/µL, p &amp;lt; 0.001] and neutrophils [0.9 (0.3, 1.4) and 0.9 (0.3, 1.4) x103/µL, p &amp;lt; 0.001] in both groups after exercise. There was no difference within and between groups for EPCs before and after the aerobic exercise session - delta 0.02 (-0.04, 0.08) among controls and 0.00 (-0.01, 0.01) among individuals with T1DM]. No difference was observed in the levels of TNF-α among controls [210.2 (142.1 - 401.2); 191.3 (136.4 - 350.5) pg/mL] and individuals with T1DM [463.8 (201.4 - 4306.0); 482.7 (143.8 – 4304.3) pg/mL], before and 60 minutes after the exercise session, respectively. The IL-6 did not show any difference in controls [148.2 (147.5 – 148.6); 148.2 (147.7 – 148.6) pg/mL] and in those with T1DM [147.2 (145.9 – 147.7); 147.2 (146.8 – 147.8) pg/mL], before and 60 minutes after exercise, respectively. Patients with T1DM and healthy controls did not show a different response on EPCs levels after an acute session of aerobic exercise, most likely because they do not have a chronic inflammatory state. Hence, our study suggests that aerobic exercise (peak of 60% VO2) has the same effect on endothelial function in patients with or without T1DM. Presentation: Saturday, June 17, 2023

Investigation of the relationship between intradialytic hypotension during hemodialysis and serum syndecan-1 concentration

Intradialytic hypotension and arrhythmias are complications of hemodialysis. They are associated with decreased intravascular volume due to reduced ultrafiltration volume, cardiac function, and arterial tone. The vascular endothelial glycocalyx, which exists on the surface of healthy vascular endothelial cells and maintains vascular permeability, has been suggested to be impaired by hemodialysis. This single-center retrospective study evaluated the association between syndecan-1, an endothelial glycocalyx dysfunction marker, and complications of hemodialysis. We enrolled 92 patients who underwent outpatient hemodialysis at Gifu Seiryu Hospital from April to July 2022 (346 hemodialysis sessions). The median duration and time of hemodialysis were 40 months and 4.1 h, respectively. Median serum syndecan-1 levels were 67.7 ng/mL before and 98.3 ng/mL after hemodialysis. Hemodialysis complications were noted in 68 sessions, all of which were hypotension. No correlation between pre-hemodialysis syndecan-1 levels and the incidence of complications was observed. However, a positive correlation between the amount of change in syndecan-1 levels before and after hemodialysis and the incidence of hemodialysis complications was noted. Conversely, syndecan-1 levels did not correlate with brain or atrial natriuretic peptides, suggesting that impairment of the vascular endothelial glycocalyx may be a possible cause of intradialytic hypotension and may be useful in preventing intradialytic hypotension.