Levels Of Endothelial Adhesion Molecules Research Articles

Glomerular deposition of galactose-deficient IgA1-containing immune complexes via glomerular endothelial cell injuries.

ABSTRACTBackgroundGalactose-deficient immunoglobulin A1 (Gd-IgA1) plays a crucial role in the development of IgA nephropathy (IgAN). However, the pathological role of Gd-IgA1-containing immune complexes (ICs) and the mechanism of deposition in the mesangial region remain unclear.MethodsTo examine the deposition of Gd-IgA1-containing ICs in the mesangial region through glomerular endothelial cell injury, we evaluated the alteration of renal microvascular endothelial glycocalyx in nude mice injected with Gd-IgA1-IgG ICs. Human renal glomerular endothelial cells (HRGECs) were used to assess the potential capacity of Gd-IgA1-IgG ICs to activate endothelial cells.ResultsNude mice injected with Gd-IgA1-containing ICs showed podocyte and endothelial cell injuries, with IgA, IgG and C3 depositions in glomerular capillaries and the mesangium. Moreover, albuminuria and hematuria were induced. Real-time glycocalyx imaging showed that renal microvascular glycocalyx was decreased immediately after injection of Gd-IgA1-containing ICs and then mesangial IgA deposition was increased. After coculture of Gd-IgA1-containing ICs with HRGECs, messenger RNA expression levels of endothelial adhesion molecules and proinflammatory mediators were upregulated significantly.ConclusionGd-IgA1-IgG ICs had a high affinity for glomerular endothelial cells, which resulted in glomerular filtration barrier dysfunction mediated by glycocalyx loss. Furthermore, Gd-IgA1-IgG ICs accelerated the production of adhesion factors and proinflammatory cytokines in glomerular endothelial cells. The glomerular endothelial cell injury induced by Gd-IgA1-containing ICs may enhance the permeability of Igs in the mesangial region and subsequent inflammatory responses in the pathogenesis of IgAN.

Sirt7 associates with ELK1 to participate in hyperglycemia memory and diabetic nephropathy via modulation of DAPK3 expression and endothelial inflammation

Diabetic nephropathy (DN) is one of the most serious complications of advanced diabetes, and increases patient mortality. Recently, epigenetics-mediated hyperglycemic memory in pathological process of DN has received attention. The purpose of this study was to determine the underlying mechanism by which sirt7 modulates hyperglycemic memory in DN. In glomerular endothelial cells (GECs) cultured in high glucose and glomeruli of DN patients and rats, an increase in p65 phosphorylation and endothelial adhesion molecule levels persisted after glucose normalization but was reversed by glucose normalization associated with death-associated protein kinase-3 (DAPK3) knockout or DAPK3 inhibitor. High glucose-mediated decrease in sirt7, the deacetylase modulating H3K18-acetylation (H3K18ac), was sustained after normoglycemia. Sirt7 overexpression accompanied by glucose normalization suppressed DAPK3 expression and inflammation in GECs. Moreover, sh-sirt7-induced inflammation was inhibited by si-DAPK3. Furthermore, sirt7 and H3K18ac were located at the DAPK3 promoter region. ELK1 was found to combine with sirt7. si-ELK1 supplemented with normoglycemia inhibited high glucose-induced DAPK3 expression and inflammation in GECs. ELK1 overexpression-mediated inflammation was inhibited by si-DAPK3. In addition, ELK1 and sirt7 were located at the same promoter region of DAPK3. ELK1 overexpression enhanced DAPK3 promoter activity, which disappeared after specific binding site mutation. In vivo, sirt7 overexpression decreased inflammation and improved renal function during insulin treatment of DN rats, whereas insulin alone did not work. Our data demonstrated high glucose-mediated mutual inhibition between sirt7 and ELK1 induced DAPK3 transcription and inflammation despite normoglycemia in GECs, thus forming a vicious cycle and participating in the occurrence of hyperglycemic memory in DN.

Influence of hydroxychloroquine blood levels on adhesion molecules associated with endothelial dysfunction in patients with systemic lupus erythematosus

BackgroundPatients with SLE have an endothelial dysfunction (ED), which is considered the earliest marker of cardiovascular (CV) disease. Endothelial cell activation induced by proinflammatory cytokines is defined by the endothelial...

Inhibition of Phosphoinositide 3-Kinase Gamma Protects Endothelial Cells via the Akt Signaling Pathway in Sepsis-Induced Acute Kidney Injury

Introduction: Sepsis is a primary cause of death in critically ill patients and is characterized by multiple organ dysfunction, including sepsis-induced acute kidney injury (AKI), which contributes to high mortality in sepsis. However, its pathophysiological mechanisms remain unclear. The kidney has one of the richest and most diversified endothelial cell populations in the body. This study was designed to investigate the effects of endothelial dysfunction in sepsis-induced AKI and explore possible intervention measures to offer new insight into the pathogenesis and treatment of sepsis-induced AKI. Methods: The circulating levels of endothelial adhesion molecules were detected in patients with sepsis and healthy controls to observe the role of endothelial damage in sepsis and sepsis-induced AKI. A murine sepsis model induced by cecal ligation and perforation was pretreated with a phosphoinositide 3-kinase gamma (PI3Kγ) inhibitor (CZC24832), and survival, kidney damage, and renal endothelial injury were assessed by pathological examination, immunohistochemistry, quantitative polymerase chain reaction, and Western blotting. Lipopolysaccharides and CZC24832 were administered to human umbilical vein endothelial cells in vitro, and endothelial cell function and the expression of adhesion molecules were evaluated. Results: Endothelial damage was more serious in sepsis-induced AKI than that in non-AKI, and the inhibition of PI3Kγ alleviates renal endothelial injury in a murine sepsis model, protecting endothelial cell function and repairing endothelial cell injury through the Akt signaling pathway. Conclusions: In this study, endothelial cell dysfunction plays an important role in sepsis-induced AKI, and the inhibition of PI3Kγ alleviates endothelial cell injury in sepsis-induced AKI through the PI3Kγ/Akt pathway, providing novel targets for treating sepsis and related kidney injury.

Subclinical markers of cardiovascular toxicity of benzene inhalation in mice

Benzene is a ubiquitous environmental pollutant. Recent population-based studies suggest that benzene exposure is associated with an increased risk for cardiovascular disease. However, it is unclear whether benzene exposure by itself is sufficient to induce cardiovascular toxicity. We examined the effects of benzene inhalation (50 ppm, 6 h/day, 5 days/week, 6 weeks) or HEPA-filtered air exposure on the biomarkers of cardiovascular toxicity in male C57BL/6J mice. Benzene inhalation significantly increased the biomarkers of endothelial activation and injury including endothelial microparticles, activated endothelial microparticles, endothelial progenitor cell microparticles, lung endothelial microparticles, and activated lung and endothelial microparticles while having no effect on circulating levels of endothelial adhesion molecules, endothelial selectins, and biomarkers of angiogenesis. To understand how benzene may induce endothelial injury, we exposed human aortic endothelial cells to benzene metabolites. Of the metabolites tested, trans,trans-mucondialdehyde (10 μM, 18h) was the most toxic. It induced caspases-3, -7 and -9 (intrinsic pathway) activation and enhanced microparticle formation by 2.4-fold. Levels of platelet-leukocyte aggregates, platelet macroparticles, and a proportion of CD4+ and CD8+ T-cells were also significantly elevated in the blood of the benzene-exposed mice. We also found that benzene exposure increased the transcription of genes associated with endothelial cell and platelet activation in the liver; and induced inflammatory genes and suppressed cytochrome P450s in the lungs and the liver. Together, these data suggest that benzene exposure induces endothelial injury, enhances platelet activation and inflammatory processes; and circulatory levels of endothelial cell and platelet-derived microparticles and platelet-leukocyte aggregates are excellent biomarkers of cardiovascular toxicity of benzene.

Endothelial adhesion molecules and multiple organ failure in patients with severe sepsis

ObjectiveTo determine if serum levels of endothelial adhesion molecules were associated with the development of multiple organ failure (MOF) and in-hospital mortality in adult patients with severe sepsis. DesignThis study was a secondary data analysis of a prospective cohort study. SettingPatients were admitted to two tertiary intensive care units in San Antonio, TX, between 2007 and 2012. PatientsPatients with severe sepsis at the time of intensive care unit (ICU) admission were enrolled. Inclusion criteria were consistent with previously published criteria for severe sepsis or septic shock in adults. Exclusion criteria included immunosuppressive medications or conditions. InterventionsNone. MeasurementsBaseline serum levels of the following endothelial cell adhesion molecules were measured within the first 72h of ICU admission: Intracellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Vascular Endothelial Growth Factor (VEGF). The primary and secondary outcomes were development of MOF (⩾2 organ dysfunction) and in-hospital mortality, respectively. Main resultsForty-eight patients were enrolled in this study, of which 29 (60%) developed MOF. Patients that developed MOF had higher levels of VCAM-1 (p=0.01) and ICAM-1 (p=0.01), but not VEGF (p=0.70) compared with patients without MOF (single organ failure only). The area under the curve (AUC) to predict MOF according to VCAM-1, ICAM-1 and VEGF was 0.71, 0.73, and 0.54, respectively. Only increased VCAM-1 levels were associated with in-hospital mortality (p=0.03). These associations were maintained even after adjusting for APACHE and SOFA scores using logistic regression. ConclusionsHigh levels of serum ICAM-1 was associated with the development of MOF. High levels of VCAM-1 was associated with both MOF and in-hospital mortality.

Glutamine supplementation attenuates expressions of adhesion molecules and chemokine receptors on T cells in a murine model of acute colitis.

Background. Migration of T cells into the colon plays a major role in the pathogenesis in inflammatory bowel disease. This study investigated the effects of glutamine (Gln) supplementation on chemokine receptors and adhesion molecules expressed by T cells in mice with dextran sulfate sodium- (DSS-) induced colitis. Methods. C57BL/6 mice were fed either a standard diet or a Gln diet replacing 25% of the total nitrogen. After being fed the diets for 5 days, half of the mice from both groups were given 1.5% DSS in drinking water to induce colitis. Mice were killed after 5 days of DSS exposure. Results. DSS colitis resulted in higher expression levels of P-selectin glycoprotein ligand- (PSGL-) 1, leukocyte function-associated antigen- (LFA-) 1, and C-C chemokine receptor type 9 (CCR9) by T helper (Th) and cytotoxic T (Tc) cells, and mRNA levels of endothelial adhesion molecules in colons were upregulated. Gln supplementation decreased expressions of PSGL-1, LFA-1, and CCR9 by Th cells. Colonic gene expressions of endothelial adhesion molecules were also lower in Gln-colitis mice. Histological finding showed that colon infiltrating Th cells were less in the DSS group with Gln administration. Conclusions. Gln supplementation may ameliorate the inflammation of colitis possibly via suppression of T cell migration.

Role of inflammation in the pathogenesis of heart failure with preserved ejection fraction and its potential as a therapeutic target

Heart failure (HF) with preserved ejection fraction (HFPEF) is an increasingly prevalent clinical syndrome with many unresolved issues regarding diagnosis, pathophysiology, and treatment. The major pathophysiological mechanisms underlying HFPEF are known to be fibrosis and reduced ventricular compliance, and hypertension (HTN) is perhaps the most significant risk factor for the development of left ventricular diastolic dysfunction (LVDD). Inflammation is one of the earliest events in cardiac stress situations such as pressure and/or volume overload and involves elevated levels of endothelial adhesion molecules as well as increased production and release of inflammatory cytokines and chemokines in the tissue. The latter promotes the infiltration of activated inflammatory cells, particularly monocytes, into the cardiac tissue. Increased monocyte infiltration is seen in the early and late stages of HTN and HFPEF. Once inside the tissue, monocytes differentiate into macrophages and promote cardiac inflammation, tissue injury, and myocardial fibrosis. This review focuses on inflammation as the initial and primary trigger of ventricular remodelling in HTN and LVDD, affecting progression to HFPEF. The link between inflammation and b-type natriuretic peptide (BNP), a clinical marker of cardiac pressure overload which is positively associated with cardiac dysfunction and HF, is also described. Finally, current and prospective therapeutic approaches for HFPEF based on modification of the inflammatory response are reviewed.

Vascular endothelial cell-derived endothelin-1 mediates vascular inflammation and neointima formation following blood flow cessation

Although endothelin-1 (ET-1) has been suggested to contribute to the pathogenesis of neointima formation and atherosclerosis, the individual roles of ET-1 derived from certain cell types in this disease remain unclear. In this study, we determined the role of vascular endothelial ET-1 on vascular inflammation and neointima formation using vascular endothelial ET-1-knockout [ET-1(f/f); Tie2-Cre (+)] mice. Intimal hyperplasia was induced by complete ligation of the left carotid artery in 12-week-old male ET-1(f/f);Tie2-Cre (+) mice (n = 35) and the wild-type (WT) littermates (n = 34). Following this intervention, neointima formation was reduced in ET-1(f/f);Tie2-Cre (+) mice compared with the WT mice, independent of the difference in blood pressure. This reduction was associated with a decrease in inflammatory cell recruitment to the vessel wall, which was accompanied by reduced expression levels of endothelial adhesion molecules as well as chemokines and a decrease in vascular smooth muscle cell proliferation. The results of our study provide direct evidence for the role of vascular endothelial ET-1 in mediating vascular inflammation and neointima formation following vascular injury in addition to promoting vasoconstriction and cell proliferation. Furthermore, this study suggests a strategy for the efficient design of ET receptor antagonists with targeted inhibition of ET-1 signalling in vascular endothelial cells.

Effects of antioxidant supplementation on insulin sensitivity, endothelial adhesion molecules, and oxidative stress in normal-weight and overweight young adults

The objective of the study was to determine whether short-term antioxidant (AOX) supplementation affects insulin sensitivity, endothelial adhesion molecule levels, and oxidative stress in overweight young adults. A randomized, double-blind, controlled study tested the effects of AOXs on measures of insulin sensitivity (homeostasis model assessment [HOMA]) and quantitative insulin sensitivity check index), endothelial adhesion molecules (soluble intercellular adhesion molecule–1, vascular adhesion molecule, and endothelial-leukocyte adhesion molecule–1), adiponectin, and oxidative stress (lipid hydroperoxides) in overweight and normal-weight individuals (N = 48, 18-30 years). Participants received either AOX (vitamin E, 800 IU; vitamin C, 500 mg; β-carotene, 10 mg) or placebo for 8 weeks. The HOMA values were initially higher in the overweight subjects and were lowered with AOX by week 8 (15% reduction, P = .02). Adiponectin increased in both AOX groups. Soluble intercellular adhesion molecule–1 and endothelial-leukocyte adhesion molecule–1 decreased in overweight AOX-treated groups by 6% and 13%, respectively (P < .05). Plasma lipid hydroperoxides were reduced by 0.31 and 0.70 nmol/mL in the normal-weight and overweight AOX-treated groups, respectively, by week 8 (P < .05). Antioxidant supplementation moderately lowers HOMA and endothelial adhesion molecule levels in overweight young adults. A potential mechanism to explain this finding is the reduction in oxidative stress by AOX. Long-term studies are needed to determine whether AOXs are effective in suppressing diabetes or vascular activation over time.

Potential Clinical Usefulness of Endothelial Adhesion Molecules in Predicting Risk of Type 2 Diabetes

Early endothelial dysfunction is a common antecedent of the metabolic or insulin resistance syndrome and may thus play an etiologic role in the pathogenesis of type 2 diabetes mellitus and associated complications. Elevated circulating levels of some endothelial adhesion molecules including e-selectin, intercellular adhesion molecule-1 (icam-1), and vascular cell adhesion molecule-1 (vcam-1) may reflect structural microvascular changes related to the pathophysiological processes of impaired insulin action and secretion. Elevated levels of soluble cellular adhesion molecules have been related to insulin resistance and other metabolic syndrome components. Evidence from prospective studies indicates that endothelial biomarkers, particularly e-selectin, may independently predict risk of type 2 diabetes among nondiabetic individuals in multiple populations. Circulating levels of endothelial adhesion molecules appear to have clinically significant prognostic value beyond inflammatory marker-crp in predicting future risk of type 2 diabetes.

Carotid Atherosclerosis and Endothelial Cell Adhesion Molecules as Predictors of Long-Term Outcome in Chronic Hemodialysis Patients

Background/Aims: Cardiovascular disease (CVD) remains the leading cause of increased morbidity and mortality for hemodialysis (HD) patients. The aim of this study was to investigate the predictive values of carotid artery atherosclerotic lesions and endothelial adhesion molecule levels for long-term outcome in non-diabetic HD patients. Methods: 112 HD patients (60 male, mean age 59 years) consecutively entered the study. Atherosclerotic disease was assessed by measuring the mean and maximum intima-media thickness (IMT and IMT_max respectively) of the common carotid arteries using an ultrasound scanner. Circulating intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels were measured by ELISA. Patients were followed for the next 5 years and primary end points on follow-up were all-cause death, death from CVD causes and incidence of a CVD event. Results: Kaplan-Meier analysis showed that survival curves for all-cause mortality, CVD mortality and morbidity differed significantly between the upper and lower tertiles of baseline IMT (p = 0.002, p = 0.01 and p = 0.001 respectively) and IMT_max values (p = 0.0007, p = 0.006 and p = 0.0003 respectively), as well as ICAM-1 (p = 0.008, p = 0.003 and p = 0.02 respectively) and VCAM-1 levels (p = 0.004, p = 0.012 and p = 0.025 respectively). In non-adjusted analysis all-cause mortality and CVD mortality and morbidity were significantly associated with IMT (p = 0.003, p = 0.01 and p = 0.001 respectively) and IMT_max values (p = 0.001, p = 0.007 and p = 0.0007 respectively). After adjusting for other significant covariates, IMT values remained associated only with CVD morbidity (p = 0.03), while IMT_max were associated with both CVD mortality and morbidity (p = 0.03 and p = 0.01 respectively). All-cause mortality and CVD mortality and morbidity were also significantly associated with serum ICAM-1 (p = 0.004, p = 0.005 and p = 0.01 respectively) and VCAM-1 levels (p = 0.008, p = 0.02 and p = 0.03 respectively). After adjusting for the same covariates, the associations between ICAM-1 and all-cause mortality and CVD mortality and morbidity remained significant (p = 0.02, p = 0.01 and p = 0.02 respectively), while serum VCAM-1 levels were independently associated only with all-cause mortality (p = 0.02). Conclusions: In non-diabetic HD patients, carotid atherosclerosis and adhesion molecule levels are independent predictors of long-term clinical outcomes and may be useful surrogate markers for risk stratification in these patients.

Circulating Levels of Endothelial Adhesion Molecules and Risk of Diabetes in an Ethnically Diverse Cohort of Women

Elevated circulating levels of soluble adhesion molecules as markers of endothelial dysfunction have been related to insulin resistance and its associated metabolic abnormalities. However, their associations with type 2 diabetes remain inconclusive. We conducted a prospective nested case-control study to examine the associations between plasma levels of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) and diabetes risk among 82,069 initially healthy women aged 50-79 years from the Women's Health Initiative Observational Study. During a median follow-up of 5.9 years, 1,584 incident diabetes case subjects were matched with 2,198 control subjects by age, ethnicity, clinical center, time of blood draw, and follow-up time. Baseline median levels of the biomarkers were each significantly higher among case subjects than among control subjects (E-selectin, 49 vs. 37 ng/ml; ICAM-1, 324 vs. 280 ng/ml; and VCAM-1, 765 vs. 696 ng/ml [all P values <0.001]). After adjustment for risk factors, the relative risks of diabetes among women in the highest quartile versus those in the lowest quartile were 3.46 for E-selectin (95% CI 2.56-4.68; P for trend <0.0001), 2.34 for ICAM-1 (1.75-3.13; P for trend <0.0001), and 1.48 for VCAM-1 (1.07-2.04; P for trend = 0.009). E-selectin and ICAM-1 remain significant in each ethnic group. In conclusion, higher levels of E-selectin and ICAM-1 were consistently associated with increased diabetes risk in a multiethnic cohort of U.S. postmenopausal women, implicating an etiological role of endothelial dysfunction in the pathogenesis of type 2 diabetes.

Effects of Benzafibrate and Simvastatin on endothelial activation and lipid peroxidation in hypercholesterolemia: evidence of different vascular protection by different lipid-lowering treatments

Conclusion: Circulating levels of endothelial adhesion molecules in hypercholesterolemic patients are decreased with Simvastatin but not Benzafibrate. Summary: Endothelial adhesion moleculeNmediated leukocyte adhesion and transendothelial migration are fundamental steps in atherogenesis. The authors studied the effects in hypercholesterolemic patients of two lipid-lowering agents on circulating levels of endothelial adhesion molecules. Never-treated hypercholesterolemic outpatients (n = 67) and 32 controls matched for sex, age, blood pressure, inflammatory indexes, and acute phase reactive proteins were studied. Hypercholesterolemic patients were divided into four groups. Group 1 was treated with simvastatin (40mg/d), group 2 received benzafibrate (80mg/d), group 3 was treated with simvastatin plus vitamin E, and group 4 was treated with benzafibrate plus vitamin E. Circulating levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin were evaluated at baseline in all four patient groups and controls, and in the four patient groups following 1, 3, 4, and 6 months of treatment. Circulating ICAM-1, VCAM-1, and E-selectin levels were higher in the hypercholesterolemic patient groups (groups 1-4) than in control subjects. Both simvastatin (group 1) and benzafibrate (group 2), significantly reduced total and low-density lipoprotein (LDL) cholesterol concentrations (P < .0001). Simvastatin treatment was more effective than benzafibrate. Vitamin E supplementation did not further reduce total or LDL cholesterol levels in either simvastatin- or benzafibrate-treated patients. Plasma ICAM-1, VCAM-1, and E-selectin significantly decreased during the 6 months of the simvastatin treatment (P < .0001). There was no decrease in endothelial adhesion molecule levels in patients treated with benzafibrate alone. The addition of vitamin E resulted in further decreases in endothelial adhesion molecules in patients treated with simvastatin and in a decrease in endothelial adhesion molecules in the patients treated with benzafibrate (P < .0003 to P < .0001). Comment: The data demonstrate drug-induced cholesterol lowering is not necessarily associated with a reduction of endothelial activation in hypercholesterolemic patients. The beneficial effects of statin therapy in treatment of patients with hypercholesterolemia may be independent of, or additive to, cholesterol-lowering effects.

The effect of alcohol consumption on endothelial adhesion molecule expression.

Endothelial adhesion molecules (AM) play an important role in the pathogenesis of several diseases namely infections, neoplasms and chronic inflammatory diseases. Because alcoholic hepatitis and even atherosclerosis are considered as inflammatory diseases and ethanol may modulate inflammatory response, several researchers have investigated the link between ethanol consumption, endothelial AM and the development of both processes. In vitro, animal and human studies have analysed the effects of ethanol and non-alcoholic components of alcoholic beverages on inflammatory biomarkers of atherosclerosis such as monocyte and endothelial AM. These studies have shown that both ethanol and non-alcoholic components of alcoholic beverages, mainly polyphenols, reduce intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression of vascular endothelium, as well as monocyte adhesion to this endothelium. These data suggest that moderate alcohol intake has an anti-inflammatory effect on the cardiovascular system and reduces early serum markers of atherosclerosis. However, at higher doses ethanol may exert an inflammatory effect. In fact, chronic alcoholics exhibit significantly higher serum levels of endothelial AM than abstainers and moderate drinkers. In addition, an upregulation of E-selectin, ICAM-1 and VCAM-1 is also detected in liver biopsies obtained from patients with alcoholic hepatitis and cirrhosis. The clinical usefulness of the measurement of serum endothelial AM is discussed.

N -3 Fatty acids plus oleic acid and vitamin supplemented milk consumption reduces total and LDL cholesterol, homocysteine and levels of endothelial adhesion molecules in healthy humans.

Background and aims: Numerous studies suggest n -3 polyunsaturated fatty acids ( n -3 PUFA) and oleic acid intake have beneficial effects on health including risk reduction of coronary heart disease. The purpose of this study was to evaluate the effect of a commercially available skimmed milk supplemented with n -3 PUFA, oleic acid, and vitamins E, B 6, and folic acid (Puleva Omega3 ®) on risk factors for cardiovascular disease. (CVD). Methods: Thirty volunteers were given 500 ml/day of semi-skimmed milk for 4 weeks and then 500 ml/day of the n -3 enriched milk for 8 further weeks. Plasma and LDL lipoproteins were obtained from volunteers at the beginning of the study ( T pre), and at 4, 8 and 12 weeks. Results: The consumption of n -3 enriched milk produced a significant decrease in plasma concentration of total and LDL cholesterol accompanied by a reduction in plasma levels of homocysteine. Plasma and LDL oxidability and vitamin E concentration remained unchanged throughout the study. A significant reduction in plasma levels of vascular cell adhesion molecule 1, and an increase in plasma concentration of folic acid were also observed. Conclusion: Daily intake of n -3 PUFA and oleic acid supplemented skimmed milk plus folic acid and B-type vitamins has favourable effects on risk factors for CVD.

Moléculas de adhesión endoteliales ICAM-1, VCAM-1 y E-selectina en pacientes con síndrome coronario agudo

The acute inflammatory response is an important phenomenon in the pathogenesis of myocardial damage during acute coronary syndrome. Endothelial dysfunction has been found in unstable angina and acute myocardial infarction, although the results are controversial. The purpose of this study was to determine the levels of the soluble endothelial adhesion molecules ICAM-1, VCAM-1 and E-selectin, in patients with unstable angina and acute myocardial infarction, compare the results in both groups, and analyze their relation with the degree of myocardial injury. Serum concentrations of ICAM-1, VCAM-1, and E-selectin were measured in 37 control subjects and 43 patients (32 with acute myocardial infarction and 11 with unstable angina). Measurements were made at the time of admission and ten days later using commercial enzyme-linked immunoabsorbent assay (ELISA) kits (R&D Systems, UK). There was a significant increase in E-selectin (p < 0.05) in patients with unstable angina at admission and ten days later. In contrast, patients with acute myocardial infarction showed no significant differences in E-selectin compared with the control group at admission or ten days later. A significant increase in VCAM-1 levels was demonstrated in both groups of patients and ICAM-1 levels in acute myocardial infarction, but the concentrations of VCAM-1 and ICAM-1 in both groups of patients at admission and ten days later did not differ significantly. There was no relation between soluble endothelial adhesion molecule levels and the severity of myocardial damage estimated by cardiac enzymes or electrocardiographic changes. This study indicates that serum levels of E-selectin, measured at time of admission and ten days later, could be a marker for unstable angina and might be useful in the differential diagnosis with myocardial infarction.

Levels of circulating endothelial adhesion molecules in patients with myelodysplastic syndromes

Intensity and specificity of leukocyte endothelial interaction may differ in various subtypes of myelodysplastic syndromes. To assess endothelial activation, plasma levels of endothelial adhesion molecules (E-selectin, VCAM-1 and ICAM-1) were analyzed in 65 patients with MDS using commercially available immunoassays. In MDS patients, high levels of sVCAM-1 were closely related to circulation of monocytic cells in the peripheral blood and splenic enlargement. Patients with CMML showed the highest sE-selectin, sICAM-1 and sVCAM-1 levels, whereas receptor levels in low-risk MDS (RA, RARS) were not significantly different from those in high-risk MDS (RAEB, RAEB-t). Similar receptor concentrations were measured in bone marrow aspirations and samples from peripheral blood. Based on levels of circulating endothelial adhesion molecules there is no clear-cut evidence for a general endothelial cell activation in MDS. Furthermore, levels of circulating endothelial adhesion molecules had no prognostic significance in MDS. Concerning MDS subtypes, patients with CMML demonstrate the highest endothelial activation based on cCAM levels obtained. Thus, increased leukocyte endothelial interaction may account for the higher incidence of extramedullary infiltrations in this MDS subtype.

Differential Effects of Moderate or Heavy Alcohol Consumption on Circulating Adhesion Molecule Levels

Epidemiological studies suggest that moderate but not heavy alcohol consumption provides protection against coronary heart disease. We assessed the relationship between alcohol consumption and serum levels of adhesion molecules involved in the pathogenesis of early atherosclerosis. One-hundred apparently healthy men with similar cardiovascular risk factors were divided into four groups according to ethanol intake. Moderate drinkers (20-40 g/day) showed lower serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels than abstainers (p < 0.05; both), as well as lower serum ICAM-1, VCAM-1 and E-selectin levels than heavy drinkers (p = 0.01; all). The latter also showed higher serum ICAM-1 and E-selectin levels than abstainers (p < 0.001; both). We conclude that moderate drinkers show a significant reduction of soluble endothelial adhesion molecule levels compared to abstainers and heavy drinkers, that may contribute to the protective effect of moderate alcohol consumption against atherosclerosis.

Systemic sclerosis-related Raynaud's phenomenon: effects of iloprost infusion therapy on serum cytokine, growth factor and soluble adhesion molecule levels.

Microvascular damage occurs in systemic sclerosis and is associated with increased serum levels of endothelial adhesion molecules and endothelium-associated cytokines, including vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, endothelin-1 and vascular endothelial growth factor (VEGF). Iloprost, a prostacyclin analogue, induces clinical benefit in patients suffering from scleroderma-related Raynaud's phenomenon. This study was performed to investigate the effect of iloprost infusions on endothelium activation. Serum samples from 12 patients with systemic sclerosis were examined using specific enzyme-linked immunoassays. The serum levels of sICAM-1, sVCAM-1 and soluble E-selectin were initially elevated and significantly reduced after iloprost infusions. The serum concentrations of VEGF and endothelin-1 revealed decreased levels after therapy too. These results indicate that the well-known clinical benefit of iloprost infusions on Raynaud's phenomenon is serologically detectable by a reduction of serum levels of endothelium-associated adhesion molecules, cytokines and growth factors reflecting an improvement in endothelial function.