Search Results (60)

Introduction: This study aimed to evaluate the diagnostic and prognostic value of soluble intercellular adhesion molecule-1 (sICAM-1) and galectin-3 in patients with type 2 diabetes mellitus (T2D) diagnosed with coronavirus disease 2019 (COVID-19). Participants and Method: This prospective observational study included 45 adult patients (≥18 years) with T2D and confirmed COVID-19 who were followed in the Infectious Diseases and Clinical Microbiology departments between May and June 2022. The control group consisted of 45 healthy volunteers without chronic illness who were presented to the internal medicine outpatient clinic. In addition to routine laboratory biomarkers assessed at hospital admission, the serum levels of sICAM-1 and galectin-3 were measured via ELISA kits. Results: The median age of the patients was 66 years (range: 41–77), and 23 (51.1%) were male. Hypertension was the most common comorbidity in addition to diabetes. Compared with those in the control group, the serum levels of both galectin-3 and sICAM-1 were significantly elevated in patients with COVID-19 and T2D (p < 0.001). However, there was no significant difference in galectin-3 or sICAM-1 levels between survivors and nonsurvivors (p = 0.240 and p = 0.266, respectively). Conclusion: Galectin-3 and sICAM-1 demonstrated stronger diagnostic utility than conventional biomarkers in T2D patients with COVID-19. The elevated levels of these markers may reflect the underlying systemic inflammation observed in diabetic patients with COVID-19. The strong correlation between galectin-3 and sICAM-1 suggests a potential link in their inflammatory regulation, although causality cannot be inferred. Full article

Previous research has linked both endothelial protein changes and vitamin D with infertility. This study was undertaken to investigate the association of proteins associated with endothelial function and vitamin D status in the luteal phase at day 21 in a group of non-obese women prior to in vitro fertilization (IVF) with either unexplained infertility (UI) or male factor infertility (MFI). Twenty-five non-obese Caucasian women from a UK academic center with MFI (n = 14) and UI (n = 11) were recruited. Blood was withdrawn at day 21 of the menstrual cycle at the time of mock embryo transfer. Vitamin D parameters were measured by tandem mass spectroscopy. Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for 20 protein markers of endothelial dysfunction. Baseline demographics did not differ between groups and parameters of response following IVF did not differ. Vitamins D₂ and D₃, and 1,25 Vitamin D₃ did not differ between groups. In UI, markers of endothelial activation/dysfunction were investigated; vascular cell adhesion molecule 1 (VCAM-1) decreased and this is associated with endothelial stress; vascular endothelial growth factor (VEGF) decreased and this may suggest impaired endometrial angiogenesis; while intercellular adhesion molecule 1 (ICAM-3) increased (p < 0.05) and is associated with increased immunological activity. A marker of vascular integrity, angiopoietin-1, increased while soluble angiopoietin-1 receptor (sTie-2) decreased (p < 0.05), suggesting increased vascular development. Endothelial markers of inflammation, coagulation, and endothelial progenitor cells were unchanged. Vitamin D and its metabolites show no relationship to UI, but endothelial activation/dysfunction and vascular integrity changes in VCAM-1, VEGF, sICAM-3, angiopoietin-1, and sTie-2 may contribute to UI, though the mechanisms through which they work require further evaluation; however, these protein changes have been associated with endometriosis, raising the suggestion that subclinical/undiagnosed endometriosis may have contributed to UI in these subjects. Full article

Background/Objectives: Chronic inflammation is recognized as an important risk factor for a variety of health disorders. Omega-6 polyunsaturated fatty acids (n-6 PUFAs), particularly linoleic (LA) and arachidonic acid (AA), have been shown to be either pro- or anti-inflammatory, and researchers have advocated both for and against reducing their dietary intake. This study sought to correlate the levels of ten inflammation-related biomarkers across multiple pathways with red blood cell (RBC) membrane levels of the major dietary and circulating n-6 PUFAs. Methods: We included 2777 participants (mean age: 66 ± 9 years, 54% women, 9.8% minorities) from the Framingham Offspring and minority-enriched Omni cohorts, and calculated partial correlation coefficients. Results: After multivariable adjustment, RBC LA was inversely correlated (all p ≤ 0.05) with five markers of inflammation, receptors, or pathways: C-reactive protein (r = −0.06); soluble interleukin-6 (r = −0.15); intercellular adhesion molecule-1 (r = −0.09); monocyte chemoattractant protein-1 (r = −0.07); and P-selectin (r = −0.07). RBC AA was inversely correlated (all p ≤ 0.05) with soluble interleukin-6 (r = −0.10); intercellular adhesion molecule-1 (r = −0.14); monocyte chemoattractant protein-1, and (r = −0.06); and osteoprotegerin (r = −0.07). Lipoprotein-associated phospholipase-A2 mass and activity, urinary isoprostanes, and tumor necrosis factor receptor-2 were not significantly correlated with LA or AA. Conclusions: In our large community-based study, we observed weak but statistically significant inverse associations between several types of inflammatory biomarkers with RBC n-6 PUFAs. Our findings do not support the hypothesis that omega-6 fatty acids are pro-inflammatory. Full article

Arterial stiffness indicates early atherosclerotic changes prevalent in children and adolescents with type 1 diabetes (T1D), even in those with a well–controlled disease and without additional cardiovascular risk factors. This study aimed to determine whether low–density lipoprotein (LDL) cholesterol and cytokine levels can indicate vascular stiffness in pediatric patients without conventional microangiopathic complications who are not undergoing lipid–lowering therapy. The total study group consisted of 59 pediatric patients divided into two subgroups based on their LDL cholesterol levels and matched for age, age at onset, and duration of diabetes. The investigation involved the precise measurement of several biomarkers including tumor necrosis factor (TNF–α), interleukin 35 (IL-35), interleukin 4 (IL-4), interleukin 10 (IL-10), interleukin 12 (IL-12), interleukin 18 (IL-18), vascular endothelial growth factor (VEGF), Soluble Vascular Cell Adhesion Molecule–1 (sVCAM–1), Intercellular Adhesion Molecule–1 (ICAM-1), Soluble Platelet Selectin (sP–Selectin), Advanced Glycation End Products (AGEs), and Receptors for Advanced Glycation End Products (sRAGE). Arterial stiffness was assessed by calculating pulsatility indices in the common carotid artery and the peripheral arteries in the upper and lower limbs. The comparative analysis indicated that, in the subgroup with LDL cholesterol levels below 100 mg/dL, in comparison to the subgroup with LDL above 100 mg/dL, there was a significant increase in pulsatility indices in elastic and large muscle arteries and notably higher levels of IL-35, IL-10, sVCAM–1, and ICAM-1. This study is the first to recommend the pulsatility index of elastic and large muscular arteries as an effective diagnostic tool for evaluating early atherosclerotic lesions in children and adolescents diagnosed with type 1 diabetes. Elevated LDL cholesterol levels may contribute to vascular stiffness through mechanisms related to a weakened inflammatory response, highlighting the complex interaction between lipid levels, inflammation, and vascular health in patients with type 1 diabetes. Full article

Endothelial dysfunction (ED) promotes and maintains atrial fibrillation (AF). Using a CHA2DS2-VASc score in women and men with paroxysmal AF, we aimed to determine which patients’ ED would be more pronounced. We recruited 47 females and 48 males (mean BMI 31 kg/m² and 30 kg/m², respectively) with paroxysmal AF and abnormal body mass and divided them into those with low (F < 3; M < 2) and high (F ≥ 3; M ≥ 2) CHA2DS2-VASC score. The blood samples were taken before AF ablation. Using Elisa tests, we measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule (sICAM-1), von Willebrand factor (vWF), and thrombomodulin (sTM). ED was more pronounced in females, expressed by higher endothelial cell marker concentrations: sVCAM-1 and sTM in low scores and sICAM-1 in high scores, CHA2DS2-VASc. Females were characterized by postmenopausal status, higher risk of thrombosis, lower GFR, and more frequent treatment with antiarrhythmic drugs. In contrast, males have only higher suppression of tumorigenicity 2 (ST2). In conclusion, women with paroxysmal AF exhibited more pronounced ED compared to men, regardless of their CHA2DS2-VASc scores. The soluble pro-inflammatory adhesion molecules and thrombomodulin emerge as the most sensitive biomarkers of ED elevated in females. Full article

Background: Soluble cell adhesion molecules such as sICAM-1 (soluble intercellular adhesion molecule-1), sVCAM-1 (soluble vascular cell adhesion molecule-1), and P-selectin have been implicated in cardiovascular disease pathogenesis in the general population. Cardiovascular disease is prevalent among patients with systemic sclerosis (SSc). This study aims to investigate potential associations between the serum levels of these adhesion molecules and specific cardiovascular comorbidities in SSc patients. Methods: This cross-sectional study encompassed 81 individuals with SSc. All SSc patients underwent a complete clinical evaluation. Serum sICAM-1, sVCAM-1, and P-selectin levels, lipid profiles and insulin resistance indices, and carotid ultrasound were assessed. Multivariable linear regression analyses were employed to investigate potential associations between adhesion molecule levels (sICAM, sVCAM, and P-selectin) and both SSc-specific manifestations and cardiometabolic parameters. Results: The associations of disease-related parameters with sICAM-1, sVCAM-1, and P-selectin levels were limited. Notably, only the modified Rodnan skin score exhibited a significant positive association with sVCAM-1 levels, while no such associations were observed for sICAM-1 and P-selectin. Regarding cardiovascular disease-related data, sVCAM-1 significantly correlated with higher values of insulin resistance and beta-cell function indices. In the case of P-selectin, although a trend was observed, statistical significance was not reached. Conclusions: In patients with SSc, serum values of sVCAM-1 independently correlate with insulin resistance. The assessment of CAMs in patients with SSc could serve as a valuable clinical tool for identifying individuals with increased insulin resistance and a higher risk of cardiovascular disease. Full article

The systemic inflammatory response after cardiopulmonary bypass has been widely studied. However, there is a paucity of studies that focus on the local inflammatory changes that occur in the pericardial cavity. The purpose of this study is to assess the inflammatory mediators in the pericardial fluid of patients undergoing cardiac surgery. We conducted a prospective cohort study on patients undergoing aortic valve replacement. Pericardial fluid and peripheral venous blood samples were collected after the opening of the pericardium. Additional samples were obtained from peripheral blood and the pericardial fluid shed through mediastinal drains 24 and 48 h after surgery. Levels of interleukin 1α (IL-1α), interleukin 1β (IL-1β), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in all pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included, of which 66% were males. Serum levels of IL-6, IL-8, and MCP-1 were significantly increased at 24 and 48 h after surgery. No significant changes were observed in the serum levels of the remaining mediators. A significant increase of postoperative pericardial fluid levels of IL-1α, IL-1β, IL-6, IL-8, IL-10, IFN-γ, VEGF, MCP-1, VCAM-1, and P-selectin was observed at 24 and 48 h after surgery. There is a robust systemic and pericardial inflammatory response after cardiac surgery on cardiopulmonary bypass. However, postoperative pericardial inflammatory activity shows a distinct pattern and is more marked than at the systemic level. These findings suggest that there is a compartmentalization of the inflammatory response within the pericardial cavity after cardiac surgery. Full article

The Mediterranean diet, featuring sourdough bread, shows promise in managing metabolic syndrome. This study explored the effects of two sourdough breads, with differing fermentation times but similar nutritional profiles, on inflammation, satiety, and gut microbiota composition in adults with metabolic syndrome. In a double-blind clinical trial, participants were randomized to consume either Elias Boulanger^® long-fermentation (48 h) sourdough bread (EBLong) or Elias Boulanger^® short-fermentation (2 h) sourdough bread (EBShort) over a two-month period. We assessed clinical parameters, inflammatory biomarkers, satiety-related hormones, and the richness and abundance of gut microbiota at baseline and follow-up. The participants included 31 individuals (mean age, 67, 51.6% female). EBShort was associated with reduced levels of soluble intercellular adhesion molecule (sICAM), and all participants, regardless of the intervention, exhibited a decrease in sICAM and diastolic pressure from baseline (p < 0.017). At follow-up, plasminogen activator inhibitor-1 (PAI-1) levels were lower in EBShort (−744 pg/mL; 95%CI: −282 to −1210 pg/mL) compared to EBLong. No differences in microbiota richness or abundance were observed. EBShort bread was effective in reducing some inflammation markers. The consumption of sourdough bread may offer potential benefits in reducing inflammation markers in individuals with metabolic syndrome; however, longer fermentation times did not show additional benefits. Full article

Increased immune–inflammatory activation has been repeatedly linked to etiopathogenesis and the progression of both major depressive disorder (MDD) and bipolar depression (BD). We explore the role of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in diagnostic differentiation and disorder progression in patients with MDD and BD. Serum levels of sICAM-1 and sVCAM-1 were measured in 137 patients (MDD = 93 and BD = 44) and compared with 73 healthy controls. The severity of psychopathology was assessed using the Hamilton Depression Rating Scale and Clinical Global Impression Scale. After adjustment for multiple confounders, we noticed significant downregulation of sVCAM-1 and upregulation of sICAM-1 levels in both patient groups. Decreased sVCAM-1 levels were detected in patients with acute episodes of BD when compared to MDD. Immune mediators were related to indicators of progression in both mood disorders. They also followed different post-treatment normalization patterns in MDD and BD and in relation to the stage of each disorder. Adhesion molecules could potentially be useful in discriminating between patients with MDD and BD and determining the possible progression of the disorders. Future nosological methods should include time-dependent pathoplasticity and biological correlates, at least for affective disorders. Full article

Endothelial dysfunction plays a key role in the development of liver cirrhosis. Among the biomarkers of endothelial dysfunction, the soluble form of Vascular Adhesion Protein-1 (sVAP-1) is an unconventional and less known adhesion molecule endowed also with amine oxidase activity. The aim of this study was to explore and correlate the behavior of sVAP-1 with that of the soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) and with the severity of liver cirrhosis. A cross-sectional study was carried out by enrolling 28 controls, 59 cirrhotic patients without hepatocellular carcinoma, and 56 patients with hepatocellular carcinoma (HCC), mainly caused by alcohol abuse. The levels of adhesion molecules and of the pro-inflammatory cytokines (IL-6 and TNF-αα) were determined by immunoassay and the enzymatic activity of sVAP-1 by a fluorometric assay. In non-diabetic patients without HCC, a specific behavior of sVAP-1 was highlighted. Differently from sVCAM-1, sICAM-1, and cytokines, the sVAP-1 level was significantly increased only in the early stage of disease, and then, it decreased in the last stage (866 ± 390 ng/mL vs. 545 ± 316 ng/mL, in Child–Pugh class A vs. C, respectively, p < 0.05). Bivariate analysis correlates sVAP-1 to sVCAM-1, in the absence of HCC (Spearman’s rho = 0.403, p < 0.01). Multiple linear regression analysis revealed that sVCAM-1 appears to be a predictor of sVAP-1 (β coefficient = 0.374, p = 0.021). In conclusion, in non-diabetic and non-HCC cirrhotic patients, sVAP-1 may be a potential prognostic biomarker that, together with sVCAM-1 and pro-inflammatory cytokines, may provide information on the progression of sinusoidal liver endothelium damage. Full article

While the pathology of acute hemorrhagic fever with renal syndrome (HFRS) has been widely researched, details on the chronic HFRS sequelae remain mainly unexplored. In this study, we analyzed the clinical and laboratory characteristics of 30 convalescent HFRS patients 14 years after the disease contraction, mainly emphasizing several endothelial dysfunction parameters. Convalescent HFRS patients exhibited significantly higher serum levels of erythrocyte sedimentation rate, von Willebrand factor, uric acid, C-reactive protein and immunoglobulin A when compared to healthy individuals. Furthermore, 24 h urine analyses revealed significantly lower sodium and potassium urine levels, as well as significantly higher proteinuria, microalbumin levels and β2-microglobulin levels when compared to healthy individuals. First morning urine analysis revealed significantly higher levels of hematuria in convalescent HFRS patients. None of the additional analyzed endothelium dysfunction markers were significantly different in post-HFRS patients and healthy individuals, including serum and urine P-selectin, E-selectin, soluble intercellular adhesion molecule 1, vascular intercellular adhesion molecule 1 (sVCAM-1) and vascular endothelial growth factor (VEGF). However, binary logistic regression revealed a weak association of serum sVCAM-1 and urine VEGF levels with HFRS contraction. Generally, our findings suggest mild chronic inflammation and renal dysfunction levels in convalescent HFRS patients 14 years after the disease contraction. Full article

There is paucity of studies that focus on the composition of pericardial fluid under resting conditions. The purpose of this study is to determine the levels of inflammatory mediators in pericardial fluid and their correlation with plasma levels in patients undergoing elective cardiac surgery. We conducted a prospective cohort study on candidates for elective aortic valve replacement surgery. Pericardial fluid and peripheral venous blood samples were collected after opening the pericardium. Levels of interleukin 1α (IL-1α); interleukin 1β (IL-1β); interleukin 2 (IL-2) interleukin 4 (IL-4); interleukin 6 (IL-6); interleukin 8 (IL8); interleukin 10 (IL10); tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in both pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included of which 66% were males. Serum levels of all study mediators were within normal limits. Serum and pericardial levels of IL-1 α, IL-1 β, IL-2, IL-4, and IL-10 were similar. Levels of VEGF, EGF, VCAM-2, ICAM 1, E-selectin, P-selectin, and L-selectin were significantly lower in pericardial fluid than in serum. However, levels of IL-6, IL-8, TNF-α, IFN-γ, MCP-1, and MCP-1 were significantly higher in the pericardial fluid than in serum. Under normal conditions, the pattern of distribution of different inflammatory mediators in the pericardial fluid does not reflect serum levels. This may either reflect the condition of the underlying myocardium and epicardial fat or the activity of the mesothelial and mononuclear cells present in pericardial fluid. Full article

We aimed to investigate the role of the CD40-CD40 ligand (CD40L) pathway in inflammation-mediated angiogenesis in proliferative diabetic retinopathy (PDR). We analyzed vitreous fluids and epiretinal fibrovascular membranes from PDR and nondiabetic patients, cultures of human retinal microvascular endothelial cells (HRMECs) and Müller glial cells and rat retinas with ELISA, immunohistochemistry, flow cytometry and Western blot analysis. Functional tests included measurement of blood–retinal barrier breakdown, in vitro angiogenesis and assessment of monocyte-HRMEC adherence. CD40L and CD40 levels were significantly increased in PDR vitreous samples. We demonstrated CD40L and CD40 expression in vascular endothelial cells, leukocytes and myofibroblasts in epiretinal membranes. Intravitreal administration of soluble (s)CD40L in normal rats significantly increased retinal vascular permeability and induced significant upregulation of phospho-ERK1/2, VEGF, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). sCD40L induced upregulation of VEGF, MMP-9, MCP-1 and HMGB1 in cultured Müller cells and phospo-ERK1/2, p65 subunit of NF-ĸB, VCAM-1 and VEGF in cultured HRMECS. TNF-α induced significant upregulation of CD40 in HRMECs and Müller cells and VEGF induced significant upregulation of CD40 in HRMECs. sCD40L induced proliferation and migration of HRMECs. We provide experimental evidence supporting the involvement of the CD40L-CD40 pathway and how it regulates inflammatory angiogenesis in PDR. Full article

Background and Objectives: To investigate peripheral blood flow in retinal vessels and vessel diameters after intravitreal ranibizumab injection (IRI) and the relationship between these parameters and cytokines in branch retinal vein occlusion (BRVO) with macular edema. Materials and Methods: We assessed relative flow volume (RFV) and the width of the main and branch retinal arteries and veins in the occluded and non-occluded regions before and after IRI in 37 patients with BRVO and macular edema. Measurements were made using laser speckle flowgraphy (LSFG). When performing IRI, we obtained samples of aqueous humor and analyzed them using the suspension array method to evaluate vascular endothelial growth factor (VEGF), placental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, IL-8, and interferon-inducible 10-kDa protein (IP-10). Results: In both retinal regions, before and after IRI, the RFV in the main artery and vein showed a significant correlation with the summed RFV in the respective branch vessels 1 and 2. In the occluded region, the RFV in the main vein was significantly negatively correlated with MCP-1, PDGF-AA, IL-6, and IL-8; the RFV in branch vein 1 was significantly negatively correlated with PlGF, MCP-1, IL-6, and IL-8; PDGF-AA was significantly negatively correlated with the width of the main and branch veins; and the RFVs of the main artery and vein decreased significantly from before to 1 month after IRI. Conclusions: Contrary to expectations, the study found that anti-VEGF therapy does not affect RFV in arteries and veins in patients with BRVO and macular edema. Furthermore, retinal blood flow is poor in patients with high MCP-1, IL-6, and IL-8. Finally, high PDGF-AA may result in smaller venous diameters and reduced retinal blood flow. Full article

Weight loss after bariatric surgery in obesity improves vascular function and metabolic/inflammatory profiles and reduces cardiovascular mortality but there are limited data on the effects of weight regain on vascular health. We compared the metabolic/inflammatory profiles, oxidative status, and vascular function of post-bariatric patients with a high ratio of weight regain (RWR) vs. non-surgical controls. Thirty-two post-bariatric patients [Roux-en-Y gastric bypass; aged = 44 ± 8 years, BMI = 40.1 ± 7.7 kg/m², and RWR = 58.7 ± 24.3%] and thirty controls that were BMI-, age-, and gender-matched entered the study. We collected clinical data, metabolic/inflammatory/oxidative stress circulating biomarkers, and endothelial/microvascular reactivity through Venous occlusion plethysmography and Laser speckle contrast imaging. The bariatric group exhibited lower neck circumference, fasting glucose, and triglycerides than the non-surgical group, while HDL-cholesterol was higher in the bariatric group (p < 0.001). There was no significant difference between groups for endothelial/microvascular reactivities (p ≥ 0.06). Resistin, leptin, endothelin-1, soluble forms of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1, tumor necrosis factor-α, and thiobarbituric acid reactive substances did not differ significantly between groups (p ≥ 0.09) either. The adiponectin level was higher in the bariatric compared to the non-surgical group, while interleukin-6 was lower in the bariatric group (p < 0.001). Despite the fact that endothelial/microvascular functions were not significantly different between groups, post-bariatric patients present partially preserved metabolic/inflammatory benefits even with high RWR. Full article