Levels Of Cellular Adhesion Molecules Research Articles

Cellular adhesion molecules in drug-naïve and previously medicated patients with schizophrenia-spectrum disorders

BackgroundEndothelial inflammation may be involved in the pathogenesis of schizophrenia, and cellular adhesion molecules (CAMs) on endothelial cells may facilitate leukocyte binding and transendothelial migration of cells and inflammatory factors. The aim of the present study was to assess levels of soluble cellular adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD) in patients with schizophrenia compared to healthy controls. MethodsThe study population consists of 138 patients with schizophrenia-spectrum disorder, of whom 54 were drug-naïve, compared to 317 general population controls. The potential confounders age, gender, smoking and body mass index (BMI) were adjusted for in linear regression models. ResultsThe total patient group showed significantly higher levels of ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) compared to controls. Previously medicated patients showed higher ICAM-1 levels compared to drug-naïve patients (p = 0.042) and controls (p < 0.001), and elevated VCAM-1 levels compared to controls (p < 0.001). Drug-naive patients had elevated levels of VCAM-1 (p = 0.031) compared to controls. ConclusionsIn our study, patients with schizophrenia – including the drug-naïve – have higher levels of soluble CAMs compared to healthy controls. These findings suggest activation of the endothelial system as in inflammation.

Baseline severity and soluble vascular cell adhesion molecule 1 (sVCAM-1) as biomarker predictors of short-term mortality in acute ischemic stroke.

The aim was to investigate the association between plasma levels of cellular adhesion molecules (CAMs) and risk factors, subtypes, severity and short-term mortality of acute ischemic stroke (IS), and to identify a panel of biomarkers to predict short-term mortality after IS. The prospective study evaluated 132 IS patients within 24h of their hospital admission. The baseline IS severity was assessed using the National Institutes Health Stroke Scale (NIHSS) and categorized as mild (NIHSS < 5), moderate (NIHSS 5-14) and severe (NIHSS ≥ 15). After three-month follow-up, the disability was assessed using the modified Rankin Scale (mRS); moreover, the patients were classified as survivors and non-survivors. Baseline inflammatory and anti-inflammatory cytokines and soluble CAMs were evaluated. Twenty-nine (21.9%) IS patients were non-survivors and showed higher NIHSS and soluble vascular cellular adhesion molecule 1 (sVCAM-1) than the survivors. The sVCAM-1 levels positively correlated with age, homocysteine, severity, and disability. The model #3 combining sVCAM-1 and NIHSS showed better results to predict short-term mortality with an area under the curve receiving operating characteristics (AUC/ROC) of 0.8841 [95% confidence interval (CI): 0.795-0.941] than the models with sVCAM-1 and NIHSS alone, with positive predictive value of 68.0%, negative predictive value of 91.3%, and accuracy of 86.5%. In conclusion, the combined model with baseline severity of IS and sVCAM-1 levels can early predict the prognosis of IS patients who may benefit with therapeutic measures of personalized therapy that taken into account these biomarkers. Moreover, this result suggests that VCAM-1 might be a potential target for the therapeutic strategies in IS.

Serum levels of VCAM-1 are associated with survival in patients treated with nivolumab for NSCLC.

BackgroundHigh circulating levels of cellular adhesion molecules (CAMs) in non‐small cell lung cancer (NSCLC) have been supposed to act as a negative prognostic factor. Here, we explored the predictive role of pre‐treatment levels of CAMs in previously treated patients receiving nivolumab for NSCLC.Materials and methodsSeventy one patients with advanced NSCLC, treated with nivolumab at the dose of 3 mg/kg every 14 days, were enrolled. Maximum follow‐up time was 3 years. Serum levels of Vascular Cell Adhesion Molecule‐1 (VCAM‐1) and Intracellular Adhesion Molecule‐1 (ICAM‐1) were measured at baseline and before each nivolumab administration. Endpoints of the study were a composite outcome of survival ≥2 years or absence of disease progression at the end of the follow‐up, and the overall survival.ResultsComposite outcome and overall survival were positively associated with VCAM‐1 baseline levels and with the reduction of VCAM‐1 during the treatment. After adjustment for potential confounders, the change in VCAM‐1 serum levels during the treatment was an independent predictor of overall survival.ConclusionsHigh baseline serum levels of VCAM‐1 are associated with a longer survival in patients treated with nivolumab as second line treatment for NSCLC. Surviving patients experience also a significant reduction in CAMs expression during the treatment. Hence, CAMs might be promising prognostic factors in patients with NSCLC underoing immunotherapy.

Does group-based high-intensity aerobic interval training improve the inflammatory status in patients with chronic heart failure?

Chronic heart failure (CHF) is a multifaceted syndrome associated with endothelial dysfunction and increased inflammation. Despite the existing controversies regarding the appropriate training modality, it is widely accepted that supervised cardiac rehabilitation (CR) interventions lead to proinflammatory biomarkers reduction and cellular adhesion molecules in patients with CHF. The aim of the study was to quantify the effects of 12-week group-based high-intensity aerobic interval training (HIAIT)/modified group-based HIAIT intervention (m-Ullevaal) vs. moderate continuous training (MICT) on serum levels of proinflammatory biomarkers. Single-blind, two-arm, prospective randomized controlled trial conducted on CHF outpatients performing group-based CR interventions throughout a 12-week period. The setting of the study was the Medical Center of Outpatient Rehabilitation and Sports Medicine, Plovdiv, Bulgaria. The population included a total of 120 outpatients of both genders, mean age of 63.73±6.68 years, with stable CHF (NYHA classes II to IIIB, were randomly assigned to HIAIT/ m-Ullevaal (N.=60) or to MICT (N.=60) group. Functional exercise capacity (FEC) of the eligible subjects was evaluated through 6-minute walk test (6MWT) and peak oxygen uptake. Blood samples were drawn at baseline, after 12 weeks follow-up for analyses of C-reactive protein (CRP), tumor necrosis factor-α (TNFα) and cellular adhesion molecules (CAM). Significant decreases in the serum levels of CRP (P=0.029), TNF-α (P=0.036), and vascular cell adhesion molecule-1 (VCAM-1) (P=0.040), were observed after 48 training sessions in the group-based HIAIT/m-Ullevaal intervention, except for intercellular adhesion molecule-1 (ICAM-1), which was higher in the MICT (P=0.034). FEC was significantly inversely related to CRP (r=-0.72, P<0.05), and the levels of VCAM-1 (r=-0.68, P<0.05). Both group-based CR interventions (HIAIT/m-Ullevaal and MICT) significantly reduced the serum levels of CRP, TNF- α, ICAM-1 and VCAM in patients with CHF. However, selected proinflammatory biomarkers changes and CAMs favorably decreased in the group-based HIAIT/m-Ullevaal intervention. The responses on serum levels of proinflammatory biomarkers and CAMs are dependent upon the type, intensity, and CR intervention duration. The group-based high-intensity aerobic interval training reduces significantly the proinflammatory biomarkers and cellular adhesion molecules in patients with chronic heart failure.

Obstructive Sleep Apnea Severity, Body Mass Index, and Circulating Levels of Cellular Adhesion Molecules.

To investigate the relationship between obstructive sleep apnea (OSA) severity, body mass index (BMI), and circulating levels of inflammatory adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin). A cross-sectional clinical cohort study on all consecutive adults referred to the University of British Columbia (UBC) Sleep Laboratory for a polysomnogram (PSG) for suspected OSA provided a morning blood sample. Samples were analyzed with multiplex immune assay (MilliporeSigma, CA) to assess the levels of adhesion molecules. 488 patients were studied; the majority were male (68%) with a mean age of 50yrs, mean AHI of 23 events/hour, and mean BMI of 32kg/m2. In multivariable linear regression models, all three adhesion molecules were significantly associated with BMI (E-selectin p < 0.0001; ICAM-1 p = 0.0007; VCAM-1 p = 0.0003). However, only E-selectin was independently associated with AHI (p = 0.02); there was no significant interaction between AHI and BMI for E-selectin (p = 0.33). Although all three adhesion molecules were associated with BMI, only E-selectin was independently associated with OSA severity. Future studies are needed to determine the clinical significance of the relationship between E-selectin and OSA.

Circulating adhesion molecules and associations with HbA1c, hypertension, nephropathy, and retinopathy in the Treatment Options for type 2 Diabetes in Adolescent and Youth study.

The Treatment Options for type 2 Diabetes in Adolescent and Youth study, a randomized clinical trial of three treatments for type 2 diabetes (T2DM) in youth, demonstrated treatment failure (defined as sustained HbA1c ≥8%, or inability to wean insulin after 3 months after acute metabolic decomposition) in over half of the participants. Given that binding of mononuclear cells to vascular endothelium, initiated by cellular adhesion molecules and chemokines, is an early step in vascular injury, we sought to evaluate (a) changes in cellular adhesion molecule levels during the trial; (b) effect of diabetes treatment; and (c) association of markers with HbA1c, hypertension, hypercholesterolemia, nephropathy, and retinopathy. Participants (n = 515 of 699) that had baseline assessment of adhesion molecules (monocyte chemoattractant protein-1 [MCP-1], vascular cell adhesion marker [VCAM], intercellular adhesion marker [ICAM], and E-Selectin) and at least one other assessment, measured at month 12, 24, or 36, were included. Over 1 to 3 years, significant increases in MCP-1 and decreases in VCAM (both P < .0001) concentrations were found; however, no significant interactions were identified with treatment group for any molecule. For every 1% increase in HbA1c, ICAM increased by 1.8%, VCAM by 1.5%, and E-selectin by 6.8% (all P < .0001). E-selectin increased by 3.7% and 4.2% for every 10 mm Hg increase in systolic and diastolic blood pressure, respectively (both P < .0001). ICAM was 10.2% higher and E-selectin was 15.5% higher in participants with microalbuminuria (both P < .01). There was no significant association of adhesion molecule levels with retinopathy. Concentrations of cellular adhesion molecules rise with increasing HbA1c in youth with T2DM, and are associated with blood pressure and microalbuminuria, markers of vascular injury.

Cell adhesion molecules, plasminogen activator inhibitor type 1, and metabolic syndrome in patients with psoriasis.

The objective of this study is to delineate the cellular adhesion molecule (CAM) profile and plasminogen activator inhibitor type 1 (PAI-1), and their association with metabolic syndrome (MetS) and carbohydrate metabolism biomarkers in psoriasis patients with mild and moderate severity. Sixty-seven patients with psoriasis as well as 102 healthy subjects were recruited. Insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), but not glucose, were significantly higher in psoriasis than in controls. Psoriasis was characterized by increased plasma levels of platelet endothelial cell adhesion molecule 1 (PECAM-1), vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, and PAI-1 as compared with controls. Psoriasis diagnosis could explain 59.0% of CAM and PAI-1 variance, with a particularly strong impact on E-selectin (45.6%), VCAM-1 (32.7%), and PAI-1 (24.8%). Subjects with MetS showed significantly higher E-selectin and PAI-1 than those without MetS. Using VCAM-1, E-selectin, PAI-1 (all positively), and P-selectin (inversely) in a binary regression equation, it was found that 87.6% of all patients were correctly classified with a sensitivity of 92.5% and a specificity of 84.3%. CAM and PAI-1 were correlated with carbohydrate metabolism biomarkers (glucose, insulin, and HOMA-IR). In conclusion, CAM levels are associated with psoriasis diagnosis and MetS may influence E-selectin and PAI-1 concentrations. More studies are needed to verify the causality among these factors, as well as their relation to the different degrees of disease severity.

Urinary 11-dehydro-thromboxane B2 levels are associated with vascular inflammation and prognosis in atherosclerotic cardiovascular disease

Cyclooxygenase-derived thromboxane (TxA2) and prostacyclin (PGI2) regulate atherogenesis in preclinical models. However, the relationship between TxA2 and PGI2 biosynthesis, vascular inflammation, and atherosclerotic cardiovascular disease (ASCVD) progression in humans remains unclear. The association between stable urine metabolites of thromboxane (TxA2-M) and prostacyclin (PGI2-M), circulating levels of cellular adhesion molecules (CAMs: E-selectin, P-selectin), chemokines and C-reactive protein, and the incidence of major adverse cardiovascular events (MACE) were evaluated in 120 patients with stable ASCVD on aspirin therapy. Urinary TxA2-M levels were significantly correlated with circulating P-selectin (r=0.319, p<0.001) and E-selectin (r=0.245, p=0.007) levels, and associated with higher risk of MACE (p=0.043). In contrast, PGI2-M levels were not significantly associated with CAM levels or MACE. These results provide insight into the contribution of TxA2 biosynthesis to ASCVD progression in humans, and suggest that patients with elevated TxA2-M levels may be predisposed to advanced platelet and endothelial activation and higher risk of adverse cardiovascular outcomes.

15-Lipoxygenase-1 Is Involved in the Effects of Atorvastatin on Endothelial Dysfunction.

Statins exert pleiotropic effects on endothelial cells in addition to lowering cholesterol. 15-Lipoxygenase-1 (ALOX15) has been implicated in vascular inflammation and disease. The relationship between atorvastatin and ALOX15 was investigated using a rat carotid artery balloon-injury model. Hematoxylin and eosin (HE) staining showed that ALOX15 overexpression increased the thickness of the intima-media (IMT). Immunohistochemistry and western blotting showed that atorvastatin increased the expression of cellular adhesion molecules (CAMs) but decreased the expression of endothelial nitric oxide synthase (eNOS); these effects of atorvastatin were blocked by ALOX15 overexpression. In human umbilical venous endothelial cells (HUVECs), silencing of ALOX15 enhanced the effects of atorvastatin on endothelial function. Expression levels of CAMs and Akt/eNOS/NO under oxidized low-density lipoprotein (ox-LDL) stimulation were modulated by ALOX15 inhibitor and ALOX15 small interfering RNA (siRNA). Atorvastatin abolished the activation of nuclear factor-kappa B (NF-κB) induced by ox-LDL. Exposure to ox-LDL induced upregulation of ALOX15 in HUVECs, but this effect was partially abolished by atorvastatin or the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). These results demonstrate that regulation of ALOX15 expression might be involved in the effects of atorvastatin on endothelial dysfunction.

Differential Associations between CDH13 Genotypes, Adiponectin Levels, and Circulating Levels of Cellular Adhesive Molecules.

CDH13 gene variants with lower adiponectin levels are paradoxically associated with a more favorable metabolic profile. We investigated the statistical association between CDH13 locus variants and adiponectin levels by examining 12 circulating inflammation marker levels and adiposity status in 530 Han Chinese people in Taiwan. After adjustments for clinical covariates, adiponectin levels were positively associated with soluble vascular cell adhesion molecule-1 (sVCAM1) levels and negatively associated with adiposity status and levels of C-reactive protein (CRP), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 (sICAM1). In addition, minor alleles of the CDH13 rs12051272 polymorphism were found to have lower adiponectin levels and higher CRP, sE-selectin, sICAM1, and sVCAM1 levels as well as higher body mass indices and waist circumferences in participants (all P < 0.05). In a subgroup analysis stratified by sex, significant associations between CDH13 genotypes and sE-selectin levels occurred only in men (P = 3.9 × 10−4 and interaction P = 0.005). CDH13 locus variants and adiponectin levels are associated with circulating levels of cellular adhesion molecules and adiposity status in a differential manner that interacts with sex. These results provide further evidence for the crucial role of adiponectin levels and CDH13 gene variants in immune-mediated and inflammatory diseases.

Astragaloside IV inhibits NF- κ B activation and inflammatory gene expression in LPS-treated mice.

In this study we investigated the role of astragaloside IV (AS-IV), one of the major active constituents purified from the Chinese medicinal herb Astragalus membranaceus, in LPS-induced acute inflammatory responses in mice in vivo and examined possible underlying mechanisms. Mice were assigned to four groups: vehicle-treated control animals; AS-IV-treated animals (10 mg/kg b.w. AS-IV daily i.p. injection for 6 days); LPS-treated animals; and AS-IV plus LPS-treated animals. We found that AS-IV treatment significantly inhibited LPS-induced increases in serum levels of MCP-1 and TNF by 82% and 49%, respectively. AS-IV also inhibited LPS-induced upregulation of inflammatory gene expression in different organs. Lung mRNA levels of cellular adhesion molecules, MCP-1, TNFα, IL-6, and TLR4 were significantly attenuated, and lung neutrophil infiltration and activation were strongly inhibited, as reflected by decreased myeloperoxidase content, when the mice were pretreated with AS-IV. Similar results were observed in heart, aorta, kidney, and liver. Furthermore, AS-IV significantly suppressed LPS-induced NF-κB and AP-1 DNA-binding activities in lung and heart. In conclusion, our data provide new in vivo evidence that AS-IV effectively inhibits LPS-induced acute inflammatory responses by modulating NF-κB and AP-1 signaling pathways. Our results suggest that AS-IV may be useful for the prevention or treatment of inflammatory diseases.

Levels of soluble adhesion molecules and their associations in inflammatory myositis

Vidya S. Limaye, Claudine S. Bonder, Wai Y. Sun, Susan Lester, Peter J. Roberts-Thomson And Peter Blumbergs

The Levels of the Circulating Cellular Adhesion Molecules ICAM-1, VCAM-1 and Endothelin-1 and the Flow-mediated Vasodilatation Values in Patients with Type 1 Diabetes Mellitus with Early-stage Diabetic Retinopathy

Endothelial dysfunction plays an important role in the development of diabetic retinopathy. The aim of this study was to evaluate endothelial dysfunction using different approaches in patients with type 1 diabete mellitus with early stages of diabetic retinopathy. For this purpose, we investigated the serum levels of cellular adhesion molecules, including intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1) and endothelin-1 (ET-1), which have emerged as specific markers of endothelial dysfunction, and measured the flow-mediated dilatation (FMD), a noninvasive technique used to evaluate endothelial dysfunction. The study group included 59 patients with type 1 diabetes mellitus (DM) and 30 age-matched healthy control subjects. The diabetic patients were divided into two groups according to the ophthalmoscopic findings: Group 1, composed of type 1 diabetic patients having no signs of diabetic retinopathy (DRP), and Group 2, composed of type 1 diabetic patients having findings of the early stages of nonproliferative diabetic retinopathy (NPDR). The serum levels of ET-1 (fmol/mL), ICAM-1 (ng/mL) and VCAM-1 (ng/mL) were 8.52±0.699 vs. 478.39±46.22 vs. 728.64±35.081 in the patients without retinopathy, 8.91±1.354 vs. 451.79±48.262 vs. 863.59±62.37 in the diabetic patients with NPDR and 10.73±1.04 vs. 608.15±74.92 vs. 872.95±57.63 in the control group. There were no significant differences in the serum levels of the three molecules between the groups. The FMD values were 6.51±0.46% in the diabetic patients without retinopathy, 6.66±0.29% in the diabetic patients with NPDR and 6.68±0.51% in the control group. No significant differences were found between the groups. The early stages of diabetic retinopathy cannot be considered in the evaluation of systemic markers of endothelial dysfunction.

Elevated soluble cellular adhesion molecules are associated with increased mortality in a prospective cohort of renal transplant recipients

BackgroundIncreased plasma levels of cellular adhesion molecules (CAMs) have been shown to be predictors of all cause mortality in individuals with chronic renal failure [1,2] and patients with end-stage renal disease receiving haemodialysis [3]. In renal transplant recipients the predictive value of CAMs has not been well characterised. The aim of this study was to assess the relationship between CAMs and all-cause mortality during prospective follow-up of a renal transplant cohort.MethodsA total of 378 renal transplant recipients were recruited between June 2000 and December 2002. Soluble vascular CAM-1 (VCAM) and soluble intercellular CAM-1 (ICAM) were measured at baseline and prospective follow-up data was collected at a median of 2441 days after enrolment.ResultsIn univariate survival analysis the renal transplant recipients with a VCAM or ICAM concentration in the lowest third were significantly more likely to have survived at follow-up (p < 0.001 and p = 0.009 respectively). In multivariate survival analysis VCAM and ICAM remained significant independent predictors of mortality following adjustment for traditional cardiovascular risk factors, hsCRP and estimated GFR (p = 0.030 and p = 0.037 respectively).ConclusionsThe results of this prospective study are the first to show that the CAMs, ICAM and particularly VCAM, are significant independent predictors of mortality in patients with a renal transplant.

Dietary fat differentially influences regulatory endothelial function during the postprandial state in patients with metabolic syndrome: From the LIPGENE study

Objective To investigate whether endothelium-dependent vasomotor function and plasma levels of cellular adhesion molecules are affected by diets with different fat quantity and quality during the postprandial state in subjects with the metabolic syndrome (MetS). Methods Patients were randomly assigned to one of four isoenergetic diets distinct in fat quantity and quality: high-SFA (HSFA); high-MUFA (HMUFA) and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with 1.24 g/day of long chain n-3 PUFA (LC n-3 PUFA) or placebo for 12 weeks each. Flow-associated vasodilatation of the brachial artery and postprandial plasma levels of total nitrites, nitric oxide (NO) synthase, soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and P-selectin were assessed post-intervention. Results Post-intervention postprandial flow-associated vasodilatation was significantly higher after the HMUFA diet ( P < 0.05) compared to subjects adhering to the other three diets. Consistently, the postprandial NO synthase response significantly increased during the HMUFA compared with the HSFA and LFHCC (placebo) diets. Postprandial sICAM-1 levels were lower during the HMUFA than during the HSFA and LFHCC n-3 diets. Conclusions Our data support the notion that the HMUFA diet improves postprandial endothelial cell function and decreases postprandial plasma sICAM-1 concentrations in patients with the MetS. These findings suggest that the postprandial state is important for understanding possible cardio-protective effects associated with the Mediterranean diet particularly in subject with the MetS.

Synovial Inflammation in Patients with Osteonecrosis of the Femoral Head

Much of the work aimed at elucidating the pathogenesis of osteonecrosis (ON) of the femoral head has focused on bone blood supply, with little attention to the surrounding synovial tissue (ST). We hypothesized that patients with ON exhibit synovial inflammation. Using immunohistological techniques, we found that a large population of patients with ON had synovial inflammation. Moreover, a population of ON patients had inflamed ST without having an inflammatory disease co-morbidity. The inflammatory infiltrate in these patients comprised primarily CD4(+) T cells and CD68(+) macrophages, the latter of which expressed increased levels of cellular adhesion molecules. Our results suggest the presence of a previously unrecognized population of ON patients without a diagnosed inflammatory co-morbidity and a highly inflammed synovium consisting primarily of a macrophage and CD4(+) T-cell infiltrate.

Development of a human in vitro blood-nerve barrier model (94.20)

Abstract Phenotypic and functional differences exist between vascular endothelium from different tissues and between microvascular and macrovascular endothelial cells from the same tissue. Little is known about cellular interactions at the blood-nerve barrier (BNB). An in vitro BNB (IVBNB) model was developed using primary human endoneurial endothelial cells (pHEndECs) freshly isolated and purified from decedent sciatic nerves via endoneurial stripping, connective tissue enzymatic digestion and density centrifugation. pHEndECs are spindle shaped, contact inhibited, differentiate to form capillary-like tubes, are Ulex Europaeus Agglutinin 1 and von Willebrand Factor positive and endocytose acetylated low density lipoprotein. They also express alkaline phosphatase, γ-glutamyl transpeptidase, glucose transporter-1, p-glycoprotein and low levels of cellular adhesion molecules. Culturing pHEndECs on collagen coated transwell inserts was used to develop the IVBNB. High transendothelial electrical resistances (~160Ω.cm2; maximal 12 days after seeding) and low solute permeability to fluoresceinated high molecular weight (70 kDa) dextran (~0.7%) were seen. Electron microscopy demonstrated intercellular tight junctions and 50-100 nm-diameter pinocytic vesicles. These features are consistent with the BNB. This model provides an avenue to study mechanisms of leukocyte entry into peripheral nerves.

Effect of Lower Extremity Bypass Surgery on Inflammatory Reaction and Endothelial Dysfunction in Type 2 Diabetic Patients

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia and dyslipidemia. The abnormalities in nutrient metabolism and elevated inflammatory mediators resulting from DM lead to impairment of wound healing and vulnerability to infection and foot ulcers. Diabetic lower limb ischemia often leads to limb necrosis. Lower extremity bypass surgery (LEBS) is indicated to prevent limb loss in patients with critical leg ischemia. This study investigated the alteration of inflammatory and endothelium dysfunction markers before and after LEBS in DM patients. Twenty one type 2 DM patients with LEBS were included. Blood was drawn before and at 1 day and 7 days after surgery in the patients. Plasma soluble cellular adhesion molecule levels and blood leukocyte integrin expressions were measured. Also, plasma concentrations of endothelin-1 and nitric oxide were analyzed to evaluate the vascular endothelial function. The results showed that there were no significant differences in plasma cellular adhesion molecules, endothelin-1 and nitric oxide levels, nor did any differences in leukocyte integrin expressions before and after the operation. These results suggest that the efficacy of LEBS on alleviating inflammatory reaction and improving endothelial function in DM patients was not obvious.

Effect of valsartan compared with valsartan/hydrochlorothiazide on plasma levels of cellular adhesion molecules: the Val-MARC trial

Background:The Val-MARC trial showed that the angiotensin receptor blocker valsartan reduces high-sensitivity C reactive protein (hsCRP) levels, an effect that is independent of blood pressure, and seems to be neutralised...

Endothelial NF-κB As a Mediator of Kidney Damage

See related article, page 268–276 In the current issue of Circulation Research Henke and coworkers demonstrate a critical role for the transcription factor nuclear factor-kappaB (NF-κB) in the genesis of renal damage caused by hypertension.1 The authors created mice in which the NF-κB superrepressor IκBαΔN was induced in the endothelium using Cre/Lox technology. They then exposed these mice and appropriate controls to a rather complex model of hypertension involving angiotensin II infusion, high salt and inhibition of endogenous nitric oxide production. Although the NF-κB superrepressor did not prevent hypertension, it markedly diminished renal injury. Albuminuria in the NF-κB suppressed mice was reduced by half, perivascular and tubular fibrosis was decreased, TNF-α levels were diminished and the renal infiltration of inflammatory cells reduced. The study illustrates a previously unappreciated role of the endothelium and specifically endothelial NF-κB in coordinating numerous aspects of hypertensive renal damage. Prevention of hypertension and its attendant end organ damage is one of the major therapeutic aims in cardiovascular medicine. A vast amount of research has been devoted to understanding the mechanisms and pathogenesis of hypertension, but for the past two decades this knowledge has not led to new treatments. Although current drugs are effective in many patients, there are still numerous patients in whom even combination therapies are not successful.2 Moreover while we focus almost solely on bringing the blood pressure levels back to normal, the mechanisms of end-organ damage are in part independent of blood pressure and are influenced by factors such as race, socioeconomic status, diabetes, dyslipidemia and other unknown factors. This is particularly true of renal failure, which occurs much more commonly in blacks and is exacerbated by diabetes. Hypertensive end organ damage is predominantly caused by inflammatory cells such as macrophages and lymphocytes infiltrating target organs. Numerous aspects of …