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Abstract The most serious long-term effects of diabetes is peripheral artery disease (PAD) which increases the chance of developing diabetic foot ulcers, gangrene and even lower limb amputation. The clinical manifestations of PAD which are typically not revealed until symptoms like intermittent claudication, rest pain and ischemic gangrene develop, are not present in majority of diabetes mellitus patients with PAD due to diabetic peripheral neuropathy. Therefore, current study is aimed to evaluate the inflammatory and endothelial dysfunction markers with their correlation to biomarkers that can help for in-time diagnosis and efficient prognosis of developing diabetes-associated PAD. Enzyme-linked immunosorbent assay was used to evaluate the interlukin-6, interlukin-8, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in PAD with diabetes group, diabetic group and healthy individual group while biomarkers were measured by kit method. It was observed that serum IL-6, IL-8, ICAM and VCAM levels in type II diabetes mellitus (T2DM) with PAD patients were increased significantly (85.93, 597.08, 94.80 and 80.66) as compared to T2DM patients (59.52, 231.34, 56.88 and 50.19) and healthy individuals (4.81, 16.93, 5.55 and 5.16). The overall means for the parameters, IL-6, IL-8, ICAM, VCAM, urea, S/creatinine, CK-MB, AST, ALT, cholesterol, triglyceride, HDL, LDL, PT, aPTT, INR, HbA1C, and CRP within all groups were significantly (P

The most serious long-term effects of diabetes is peripheral artery disease (PAD) which increases the chance of developing diabetic foot ulcers, gangrene and even lower limb amputation. The clinical manifestations of PAD which are typically not revealed until symptoms like intermittent claudication, rest pain and ischemic gangrene develop, are not present in majority of diabetes mellitus patients with PAD due to diabetic peripheral neuropathy. Therefore, current study is aimed to evaluate the inflammatory and endothelial dysfunction markers with their correlation to biomarkers that can help for in-time diagnosis and efficient prognosis of developing diabetes-associated PAD. Enzyme-linked immunosorbent assay was used to evaluate the interlukin-6, interlukin-8, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in PAD with diabetes group, diabetic group and healthy individual group while biomarkers were measured by kit method. It was observed that serum IL-6, IL-8, ICAM and VCAM levels in type II diabetes mellitus (T2DM) with PAD patients were increased significantly (85.93, 597.08, 94.80 and 80.66) as compared to T2DM patients (59.52, 231.34, 56.88 and 50.19) and healthy individuals (4.81, 16.93, 5.55 and 5.16). The overall means for the parameters, IL-6, IL-8, ICAM, VCAM, urea, S/creatinine, CK-MB, AST, ALT, cholesterol, triglyceride, HDL, LDL, PT, aPTT, INR, HbA1C, and CRP within all groups were significantly (P < 0.05) different from each other. Therefore, it was concluded that the change in IL-6, IL-8, ICAM and VCAM can serve as an accurate diagnostic indicator and successful treatment. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still a global concern with high morbidity and mortality rates. The role of endothelial cells in the progress of COVID-19 is well established. Therefore, the current study aimed to measure the endothelial markers and their correlation with the hematological parameters in intensive care unit-admitted COVID-19 patients. This study involved 111 adult participants, including 55 ICU-admitted patients with COVID-19 and 56 healthy controls. Levels of E-selectin, ICAM-1, and VCAM-1 in the plasma of the study participants were measured and correlated with hematological parameters. The study demonstrates that COVID-19 patients admitted to the ICU have higher levels of E-selectin, ICAM-1, and VCAM-1 compared to healthy controls (p <.05). These elevated levels can serve as reliable indicators of endothelial dysfunction and early markers for the detection and prediction of endothelial cell involvement in COVID-19 complications. The findings of this study suggest that increased levels of E-selectin, VCAM-1, and ICAM-1 in patients with COVID-19 are indicative of the participation of endothelial cells in the pathogenesis of COVID-19 complications. Consequently, these endothelial markers are proposed as potential early indicators for predicting the severity of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Age-related declines in cognitive function may begin in midlife. Purpose: To determine whether blood-based biomarkers of inflammation, metabolic dysregulation and neurotoxins are associated with risk of cognitive decline and impairment. Methods: Baseline blood samples from the longitudinal Beaver Dam Offspring Study (2005–2008) were assayed for markers of inflammation, metabolic dysregulation, and environmental neurotoxins. Cognitive function was measured at baseline, 5-year (2010–2013) and 10-year (2015–2017) examinations. Participants without cognitive impairment at baseline and with cognitive data from at least one follow-up were included. Cox proportional hazards models were used to evaluate associations between baseline blood biomarkers and the 10-year cumulative incidence of cognitive impairment. Poisson models were used to estimate the relative risk (RR) of 5-year decline in cognitive function by baseline blood biomarkers. Models were adjusted for age, sex, education, and cardiovascular related risk factors. Results: Participants (N = 2421) were a mean age of 49 years and 55% were women. Soluble vascular cell adhesion molecule-1 (sVCAM-1Tertile(T)3 vs T1-2 hazard ratio (HR) = 1.72, 95% confidence interval (CI) = 1.05,2.82) and hemoglobin A1C (HR = 1.75, 95% CI = 1.18,2.59, per 1% in women) were associated with the 10-year cumulative incidence of cognitive impairment. sVCAM-1 (RRT3 vs T1-2 = 1.45, 95% CI = 1.06,1.99) and white blood cell count (RR = 1.10, 95% CI = 1.02,1.19, per 103/μL) were associated with 5-year cognitive decline. Conclusions: Biomarkers related to inflammation and metabolic dysregulation were associated with an increased risk of developing cognitive decline and impairment. These results extend previous research in cognitive aging to early markers of cognitive decline in midlife, a time when intervention methods may be more efficacious. [ABSTRACT FROM AUTHOR]

Abstract Objective The purpose of this clinical trial was to examine the effect of omega-3 fatty acids (W-3 FAs), nanocurcumin and their combination on serum levels and gene expression of VCAM in patients with episodic migraine. Results In this study, 80 patients were randomly divided in to 4 groups to receive for 2 months. Both serum levels and gene expression of VCAM showed remarkable decreases after single W-3 and after combined W-3 and nanocurcumin interventions. However, a borderline significant change and no remarkable change were observed after single nanocurcumin supplementation and in control group, respectively. While a significant difference between study groups in VCAM concentrations existed, there was no meaningful difference in VCAM gene expression among groups. It appears that the W-3 and combined W-3 and nanocurcumin can relieve VCAM serum level and its gene expression in patients with episodic migraine. Moreover, the combination of W-3 with nanocurcumin might cause more significant declines in VCAM level in the serum of migraine patients than when W-3 is administered alone. Trial Registration: This study was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: NCT02532023.

Superimposed preeclampsia complicates about 20% of pregnancies in women with chronic hypertension and is associated with increased maternal and perinatal morbidity compared with preeclampsia alone. Distinguishing superimposed preeclampsia from chronic hypertension can be challenging because, in chronic hypertension, the traditional criteria for the diagnosis of preeclampsia, hypertension, and significant proteinuria can often predate the pregnancy. Furthermore, the prevalence of superimposed preeclampsia is unlikely to be uniformly distributed across this high-risk group but is related to the severity of preexisting endothelial dysfunction. This has led to interest in identifying biomarkers that could help in screening and diagnosis of superimposed preeclampsia and in the stratification of risk in women with chronic hypertension. Elevated levels of uric acid and suppression of other renal biomarkers, such as the renin-angiotensin aldosterone system, have been demonstrated in women with superimposed preeclampsia but perform only modestly in its prediction. In addition, central to the pathogenesis of preeclampsia is a tendency toward an antiangiogenic state thought to be triggered by an impaired placenta and, ultimately, contributing to the endothelial dysfunction pathognomonic of the disease. In the general obstetrical population, angiogenic factors, such as soluble fms-like tyrosine kinase-1 and placental growth factor, have shown promise in the prediction of preeclampsia. However, soluble fms-like tyrosine kinase-1 and placental growth factor are impaired in women with chronic hypertension irrespective of whether they develop superimposed preeclampsia. Therefore, the differences in levels are less discriminatory in the prediction of superimposed preeclampsia compared with the general obstetrical population. Alternative biomarkers to the angiogenic and renal factors include those of endothelial dysfunction. A characteristic of both preeclampsia and chronic hypertension is an exaggerated systemic inflammatory response causing or augmenting endothelial dysfunction. Thus, proinflammatory mediators, such as tumor necrosis factor-α, interleukin-6, cell adhesion molecules, and endothelin, have been investigated for their role in the screening and diagnosis of superimposed preeclampsia in women with chronic hypertension. To date, the existing limited evidence suggests that the differences between those who develop superimposed preeclampsia and those who do not are, as with angiogenic factors, also modest and not clinically useful for the stratification of women with chronic hypertension. Finally, pro-B-type natriuretic peptide is regarded as a sensitive marker of early cardiac dysfunction that, in women with chronic hypertension, may predate the pregnancy. Thus, it has been proposed that pro-B-type natriuretic peptide could give insight as to the ability of women with chronic hypertension to adapt to the hemodynamic requirements of pregnancy and, subsequently, their risk of developing superimposed preeclampsia. Although higher levels of pro-B-type natriuretic peptide have been demonstrated in women with superimposed preeclampsia compared with those without, current evidence suggests that pro-B-type natriuretic peptide is not a predictor for the disease. The objectives of this review are to, first, discuss the current criteria for the diagnosis of superimposed preeclampsia and, second, to summarize the evidence for these potential biomarkers that may assist in the diagnosis of superimposed preeclampsia. [ABSTRACT FROM AUTHOR]

Objectives: To assess first trimester serum placental growth factor (PLGF), soluble fms‐like tyrosine kinase‐1 (sFLT‐1), interleukin‐6 (IL‐6), tumour necrosis factor‐α (TNF‐α), endothelin and vascular cell adhesion molecule (VCAM) in women with chronic hypertension (CH) stratified according to blood pressure (BP) control. Design: Case–control. Setting: Tertiary referral centre. Population: 650 women with CH, 142 normotensive controls. Methods: In the first trimester, patients with CH were subdivided into four groups. Group 1 included women without pre‐pregnancy CH presenting with BP ≥140/90 mmHg. Groups 2–4 had pre‐pregnancy CH; in group 2 the BP was <140/90 mmHg without antihypertensive medication, in group 3 the BP was <140/90 mmHg with antihypertensive medication, and in group 4 the BP was ≥140/90 mmHg despite antihypertensive medication. PLGF, sFLT‐1, IL‐6, TNF‐α, endothelin and VCAM were measured at 11+0–13+6 weeks' gestation and converted into multiples of the expected median (MoM) using multivariate regression analysis in the controls. Main outcome measure: Comparisons of MoM values of PLGF, sFLT‐1, endothelin, IL‐6, TNF‐α and VCAM between the entire cohort of women with CH and the control group were made using Student's t‐test or Mann–Whitney U‐test. Comparisons between the four CH groups were made using analysis of variance or Kruskal–Wallis tests. Results: Compared with the control group, women with CH had significantly lower MoM of PLGF, sFLT‐1 and IL‐6 and a significantly higher MoM of endothelin. Between the four groups of women with CH, there were no significant differences in the MoM of sFLT‐1, PLGF, sFLT‐1/PLGF ratio, endothelin, IL‐6 or VCAM, or in the levels of TNF‐ α. Conclusion: In women with CH, differences exist in first trimester angiogenic and inflammatory profiles when compared with normotensive pregnancies. However, these differences do not assist in the stratification of women with CH to identify those with more severe underlying disease and worse pregnancy outcomes. First trimester blood pressure control impacts on serum PLGF, sFLT‐1, endothelin and IL‐6 in women with chronic hypertension. First trimester blood pressure control impacts on serum PLGF, sFLT‐1, endothelin and IL‐6 in women with chronic hypertension. This article includes Author Insights, a video abstract available at: https://vimeo.com/bjog/authorinsights16835 [ABSTRACT FROM AUTHOR]

Objective: The purpose of this clinical trial was to examine the effect of omega-3 fatty acids (W-3 FAs), nanocurcumin and their combination on serum levels and gene expression of VCAM in patients with episodic migraine. Results: In this study, 80 patients were randomly divided in to 4 groups to receive for 2 months. Both serum levels and gene expression of VCAM showed remarkable decreases after single W-3 and after combined W-3 and nanocurcumin interventions. However, a borderline significant change and no remarkable change were observed after single nanocurcumin supplementation and in control group, respectively. While a significant difference between study groups in VCAM concentrations existed, there was no meaningful difference in VCAM gene expression among groups. It appears that the W-3 and combined W-3 and nanocurcumin can relieve VCAM serum level and its gene expression in patients with episodic migraine. Moreover, the combination of W-3 with nanocurcumin might cause more significant declines in VCAM level in the serum of migraine patients than when W-3 is administered alone. Trial Registration: This study was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: NCT02532023. [ABSTRACT FROM AUTHOR]

Pluchea Indica is a shrub plant found in mangrove forests. The leaves are consumed as food and herbal tea and exhibit various biological effects, such as antioxidant and anti-inflammatory activities, in macrophages and animal models. However, the inhibitory activity of P. Indica leaf extract on vascular inflammation remains unknown. Therefore, this study investigated the effect of an ethanol extract from P. Indica herbal tea leaves (PIE) on tumor necrosis factor-α (TNF-α)-induced human vascular endothelial EA.hy926 cells. The cytotoxic effect of PIE was determined by thiazolyl blue tetrazolium bromide assays. PIE at concentrations of 12.5 - 50 μg/mL did not show significant cytotoxicity, whereas PIE at concentrations ≥ 100 μg/mL decreased cell viability. PIE inhibited the production of reactive oxygen species (ROS) in TNF-α-stimulated endothelial cells. To evaluate the PIE's anti-vascular inflammatory activity, the protein expression of cell adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), was determined by western blot. PIE significantly decreased TNF-α-induced ICAM-1 and VCAM-1 expression in a concentration-dependent manner. Furthermore, PIE upregulated heme oxygenase-1 (HO-1) in a concentration- and time-dependent manner. Inhibiting the activity of HO-1 by tin protoporphyrin IX significantly blocked the suppressive effect of PIE on ICAM-1 but not VCAM-1 expression. Therefore, PIE exerts anti-inflammatory activity on vascular endothelial cells, at least in part, by suppressing ROS production and the induction of HO-1. The obtained data suggest that PIE is a promising substance for developing therapeutic agents or as an ingredient of functional food. [ABSTRACT FROM AUTHOR]

Introduction: Chronic hypertension complicates 1%‐2% of pregnancies and is one of the most significant risk factors for the development of preeclampsia. Inflammatory mediators, such as interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), vascular cell adhesion molecule (VCAM) and endothelin have been implicated in the endothelial dysfunction that is pathognomonic of preeclampsia and may serve as useful first trimester biomarkers for the prediction of preeclampsia. The objectives of this study are: first, to investigate differences in serum levels of IL‐6, TNF‐α, VCAM and endothelin at 11+0 to 13+6 weeks' gestation in women with chronic hypertension who developed superimposed preeclampsia with those who did not and normotensive controls and, second, to evaluate the performance of these biomarkers in the prediction of preeclampsia. Material and methods: The study population was comprised of 650 women with chronic hypertension, including 202 who developed superimposed preeclampsia and 448 who did not, and 142 normotensive controls matched to the chronic hypertension group for storage time and racial origin. Serum concentrations of IL‐6, TNF‐α, VCAM and endothelin were measured and the values were converted into multiples of the expected median using multivariate regression analysis in the control group. The multiples of the median values of the biomarkers between the two groups of women with chronic hypertension and the controls were compared, and the receiver operating characteristic curve (ROC) was used to assess the performance of these variables for the prediction of preeclampsia. Results: In women with chronic hypertension, compared with the normotensive controls, there was a significantly higher first trimester median concentration of endothelin but not of VCAM, IL‐6 or TNF‐α. Within the cohort of women with chronic hypertension, those who developed superimposed preeclampsia, compared with those who did not, had higher first trimester serum concentration of VCAM but not of endothelin, IL‐6 or TNF‐α. However, serum VCAM provided a poor prediction of superimposed preeclampsia (area under the ROC curve 0.537, 95% CI 0.487‐0.587). Conclusions: Women with chronic hypertension have increased serum endothelin in the first trimester of pregnancy and those who develop superimposed preeclampsia have higher levels of VCAM. None of the inflammatory mediators performed well in the first trimester in the prediction of preeclampsia. [ABSTRACT FROM AUTHOR]

Abstract Objective Systemic inflammation is a recognised contributory factor in the pathogenesis of de novo post-operative atrial fibrillation after cardiac surgery. This study aims to determine whether serum soluble vascular endothelial cell adhesion molecule (sVCAM-1) may predict the onset of POAF in patients under going coronary artery bypass grafting. Methods 34 patients undergoing non-emergent, on-pump CABG were prospectively recruited. Plasma was obtained at 24 h pre-operatively and at 48 and 96 h post-operatively. POAF was defined by continuous Holter recording. Inter-group comparisons were performed using student t-test or ANOVA as appropriate. Results Thirteen (13/34) patients developed POAF at a mean of 2.5 days post-operatively. Serum sVCAM-1 was significantly increased in the pre-operative serum of POAF when compared to non-POAF patients (p = 0.022). No significant difference was observed between the groups at 48 h (p = 0.073) or 96 h (p = 0.135) post-operatively. sVCAM-1 had a sensitivity of 60.0% and specificity of 77.27%, with an overall diagnostic accuracy of 75.2% in predicting POAF. Conclusions sVCAM-1 concentration in the pre-operative serum of patients undergoing CABG may accurately predict the onset of de novo POAF. As such, serum sVCAM-1 may be used as a predictive biomarker for this common arrhythmia. Further work must now perform prospective, targeted validation of these results in a larger patient cohort.

Objective: Systemic inflammation is a recognised contributory factor in the pathogenesis of de novo post-operative atrial fibrillation after cardiac surgery. This study aims to determine whether serum soluble vascular endothelial cell adhesion molecule (sVCAM-1) may predict the onset of POAF in patients under going coronary artery bypass grafting.Methods: 34 patients undergoing non-emergent, on-pump CABG were prospectively recruited. Plasma was obtained at 24 h pre-operatively and at 48 and 96 h post-operatively. POAF was defined by continuous Holter recording. Inter-group comparisons were performed using student t-test or ANOVA as appropriate.Results: Thirteen (13/34) patients developed POAF at a mean of 2.5 days post-operatively. Serum sVCAM-1 was significantly increased in the pre-operative serum of POAF when compared to non-POAF patients (p = 0.022). No significant difference was observed between the groups at 48 h (p = 0.073) or 96 h (p = 0.135) post-operatively. sVCAM-1 had a sensitivity of 60.0% and specificity of 77.27%, with an overall diagnostic accuracy of 75.2% in predicting POAF.Conclusions: sVCAM-1 concentration in the pre-operative serum of patients undergoing CABG may accurately predict the onset of de novo POAF. As such, serum sVCAM-1 may be used as a predictive biomarker for this common arrhythmia. Further work must now perform prospective, targeted validation of these results in a larger patient cohort. [ABSTRACT FROM AUTHOR]

The elevated cardiovascular morbidity and mortality in chronic kidney disease (CKD) is linked with endothelial dysfunction secondary to the pro-inflammatory and pro-oxidative state typical of this pathology. In consideration of the well-known pleiotropic effect of statins, we investigated the effect of cholesterol lowering treatment on endothelial dysfunction markers (MED), asymmetric dimethylarginine (ADMA), vascular cell (VCAM) and intercellular (ICAM) adhesion molecule. Plasma MED concentrations, inflammation and oxidative stress indices [Kynurenine/Tryptophan (Kyn/Trp) ratio, malondialdehyde (MDA) and allantoin/uric acid (All/UA) ratio] were measured in 30 CKD patients randomized to three cholesterol lowering regimens for 12 months (simvastatin 40 mg/day, ezetimibe/simvastatin 10/20 mg/day, or ezetimibe/simvastatin 10/40 mg/day). Treatment significantly reduced ADMA concentrations in all patients [0.694 μmol/L (0.606–0.761) at baseline vs. 0.622 μmol/L (0.563–0.681) after treatment, p < 0.001]. ADMA reduction was paralleled by a significant decrease of MDA, All/AU ratio and Kyn/Trp ratio, but not VCAM and ICAM plasma concentrations. Cholesterol lowering treatment was associated with a significant reduction in plasma ADMA concentrations in CKD patients. This might be mediated by reduced oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Paraquat (1,1’-dimethyl-4,4’-bipyridinium) (PQ), is a nonselective contact herbicide that is highly toxic to humans. The kidney is affected during PQ intoxication. Dexamethasone (Dexa) has anti-inflammatory effects and is used to treat cases of PQ poisoning. We investigated in rat kidney hemodynamic effects and immunohistochemical characteristics of Dexa treatment in acute PQ poisoning. Adult male rats were divided into four groups: 1, untreated control; 2, treated with 100 mg/kg Dexa; 3, treated with 25 mg/kg PQ; 4, treated with PQ + Dexa. Mean arterial pressure (MAP) and heart rate (HR) were recorded during the experimental period (2 h). Tissues were removed after 2 h and immunohistochemistry was performed after 24 h. Paraffin sections of kidney were prepared and anti-cyclo-oxygenase-1 (COX-1), anti-cyclo-oxygenase-2 (COX-2), anti-angiotensin converting enzyme (ACE), anti-aquaporin-1 (AQU-1), anti-vascular cell adhesion molecule (VCAM) primary antibodies were used for immunohistochemical examination. Immunoreactivities were scored as: (1) minimal, (2) weak, (3) mild, (4) moderate, (5) strong and (6) very strong. MAP and HR were measured at 10 min, 20 min, 1 h and 2 h. MAP at 10 and 20 min and 1 h was increased in the Dexa group. HR also was increased in all groups compared to controls at 2 h. Compared to groups 2 and 4, MAP values decreased significantly in group 3 at 1 h. The intensity of all of immunoreactivities was decreased in group 2. In group 3, immunoreactivities of COX-1, COX-2 and ACE were decreased compared to the control and the other groups, whereas AQU-1 and VCAM immunoreactivities were the same as the control group. ACE and VCAM immunoreactivities were decreased in group 4 compared to the control group, while COX-1, COX-2 and AQU-1 immunoreactivities were close to those of the control group. Dexa appears to be useful for treating PQ intoxication. [ABSTRACT FROM PUBLISHER]

The aim of this study was to determine whether pre-treatment with nitric oxide-loaded echogenic liposomes (NO-ELIP) plus ultrasound can improve highlighting by molecularly targeted (anti-vascular cell adhesion molecule 1 [VCAM-1]) ELIP of atheroma components. Atherosclerotic animals were treated with anti-VCAM-1-ELIP or immunoglobulin (IgG)-ELIP. Each group was selected at random to receive pre-treatment with standard ELIP plus ultrasound, NO-ELIP without ultrasound and NO-ELIP plus ultrasound. Intravascular ultrasound highlighting data for the same arterial segments were collected before and after treatment. Pre-treatment with NO-ELIP plus ultrasound resulted in a significant increase in acoustic enhancement by anti-VCAM-1-ELIP (21.3 ± 1.5% for gray-scale value, 53.9 ± 3.1% for radiofrequency data; p < 0.001 vs. IgG-ELIP, p < 0.05 vs. pre-treatment with standard ELIP plus ultrasound or NO-ELIP without ultrasound). NO-ELIP plus ultrasound can improve highlighting of atheroma by anti-VCAM-1 ELIP. This NO pre-treatment strategy may be useful in optimizing contrast agent delivery to the vascular wall for both diagnostic and therapeutic applications. [ABSTRACT FROM AUTHOR]

Background: In this study, we investigated the effect of melatonin administration on four markers of endothelial cell function including intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), C-reactive protein (CRP), and nitric oxide (NO) on patients with three vessels coronary disease. Materials and Methods: This double-blind, randomized, controlled trial study was conducted on 39 patients (32 men and 7 women) with three vessels coronary disease. The case group included 20 patients who received 10 mg oral melatonin 1 h before sleeping for 1 month. The control group included 19 patients who received placebo 1 h before sleeping for 1 month. The serum levels of CRP, ICAM, VCAM, and NO were compared after 1 month treatment. Results: After 1 month of melatonin treatment, the mean level of ICAM, VCAM, and CRP showed a statistically significant decrease in the case group. On the other hand, the mean level of VCAM increased significantly in the control group. The mean levels of CRP and ICAM were also increased in the control group, but the difference did not reach the significant threshold. With respect to NO, there was a statistically significant increase in the case group, while there was a statistically significant decrease in serum NO in the control group. Conclusions: The results of this study suggested that melatonin may have beneficial effects on endothelial oxidative stress even in patient with severe and advanced atherosclerosis.

Chemo- and radiotherapy induced thrombocytopenia present significant limitations for tumor therapy. In this study, we examined the therapeutic effect of recombinant human tyrosyl-tRNA synthetase (rhTyrRS) against development of thrombocytopenia in cyclophosphamide (CTX) treated mice. Our data indicate that intraperitoneal administration of at least 10 μg/day rhTyrRS for 7 days significantly prevents the decrease in platelets 8 days after CTX injection. The data further demonstrate that rhTyrRS promotes migration and aggregation of megakaryocytes to the bone marrow niche. Real-time PCR and flow cytometry reveal that VCAM-1 is particularly important for the adhesion. Together, these data suggest that rhTyrRS might be a useful therapeutic agent for chemotherapy-induced thrombocytopenia. [ABSTRACT FROM AUTHOR]

Long-term endotoxin challenge may promote frequent complications in dialysis patients, namely malnutrition, chronic inflammation, and atherosclerosis, which are recognized as the so-called MIA syndrome. Circulating soluble vascular cell adhesion molecule-1 (sVCAM-1) levels may be used to determine the stage of atherosclerosis. This study aimed to assess endotoxin level in hemodialysis (HD) patients and its role in inducing inflammation. The study was conducted on 50 HD patients, chosen from four dialysis centers in Alexandria. Serum blood samples were collected for the determination of albumin and C-reactive protein (CRP), and whole blood samples were used for the measurement of hemoglobin level. A heparinized whole blood sample was taken postdialysis for endotoxin assay by limulus amebocyte lysate test, and in addition to sVCAM-1 was estimated using enzyme-linked immunosorbent assay. The mean endotoxin level was 76.30 pg/mL;80% exhibited values higher than 60 pg/mL. Half the studied patients had CRP values that exceeded the upper limit of the laboratory reference range (<6.0 mg/L). A statistically significant correlation was found between endotoxin and CRP levels (r=0.47, P=0.001). The mean pre-HD level of VCAM was 1851.00 ng/mL, while the mean post-HD level was 2829.00 ng/mL with statistically significant correlation (r = 0.354, P = 0.012) and it also correlated significantly with endotoxin as well as CRP levels. Endotoxemia may play an important role in the aggravation of endothelial dysfunction in HD patients as indicated by the post-HD rise in sVCAM-1. [ABSTRACT FROM AUTHOR]

Quantitative detection of proteins in multiplexed platforms presents technical advantages at clinical and laboratory settings compared to the monoplex ELISA method. With this purpose, we implemented a pilot study using in-house–designed sandwich-type antibody array for multiplexed detection of seven cardiovascular disease (CVD) risk markers and compared the performance of our immunosensor to conventional ELISA kits. Results indicated that our immunosensor can determine serum amyloid A (SAA), vascular cell adhesion molecule (VCAM), and myoglobin (MYO) concentrations accurately, precisely, and above all very much similar to ELISA. Hence, multiplexed detection and quantification of SAA, VCAM, and MYO with our immunosensor can be considered as a potential multiplexed alternative to the ELISA method. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Vascular cell adhesion molecule (VCAM-1) plays a critical role in the inflammatory processes by stimulating the recruitment, extravasation, and migration of leukocytes. Its expression and regulation in the dental pulp is not well elucidated. Methods: Primary dental pulp cells were exposed to prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), or interleukin 1β (IL-1β) with/without aspirin. VCAM-1 messenger RNA expression was analyzed by reverse transcriptase–polymerase chain reaction. Soluble VCAM-1 (sVCAM-1) in the culture medium was determined by enzyme-linked immunosorbent assay, and the number of viable cells was estimated by (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Results: IL-1β induced VCAM-1 gene expression of pulp cells. IL-1β also stimulated sVCAM-1 production. The IL-1β–induced sVCAM-1 production was not inhibited but rather enhanced by aspirin, a cyclooxygenase (COX) inhibitor. PGE2 and PGF2α decreased the VCAM-1 expression and sVCAM-1 production of pulp cells. U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene), a mitogen-activated protein kinase kinase (MEK) inhibitor, attenuated IL-1β–induced sVCAM-1 production. However, no marked cytotoxicity was noted in these experimental conditions as analyzed by MTT assay. Conclusions: IL-1β may be involved in the pulpal inflammatory processes via stimulation of VCAM-1 expression and sVCAM-1 production. This event is not mediated by COX activation and prostanoid production but is associated with MEK signaling. PGE2 and PGF2α may potentially regulate inflammatory processes by the inhibition of VCAM-1. [Copyright &y& Elsevier]

Abstract: Aims: The expression of cell adhesion molecules on vascular smooth muscle cells is central to leukocyte recruitment and progression of atherosclerotic disease. Ohioensin F, a chemical compound of the Antarctic moss Polyerichastrum alpinum, exhibited inhibitory activity against protein tyrosine phosphatase 1B and antioxidant activity. However, published scientific information regarding other biological activities and pharmacological function of ohioensin F is scarce. In the present study, we aimed to examine the in vitro effects of ohioensin F on the ability to suppress TNF-α-induced adhesion molecule expression in vascular smooth muscle cells (VSMCs). Main methods: The inhibitory effect of ohioensin F on TNF-α-induced upregulation in expression of adhesion molecules was investigated by enzyme-linked immunosorbent assay, cell adhesion assay, RT-PCR, western blot analysis, immunofluorescence, and transfection and reporter assay, respectively. Key findings: Pretreatment of VSMCs with ohioensin F at nontoxic concentrations of 0.1–10μg/ml dose-dependently inhibited TNF-α-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). In addition, ohioensin F suppressed adhesion of THP-1 monocytes to TNF-α-stimulated VSMCs. Ohioensin F reduced TNF-α-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38, ERK, JNK and Akt. Finally, ohioensin F inhibited TNF-α-induced CAM mRNA expression and NK-κB translocation. Significance: These results suggest a new mechanism of ohioensin F''s anti-inflammatory action, owing to the negative regulation of TNF-α-induced adhesion molecule expression, monocyte adhesion and ROS production in vascular smooth muscle cells. Our finding also supports ohioensin F as a potential pharmacological, anti-inflammatory molecule that has a protective effect on the atherosclerotic lesion. [Copyright &y& Elsevier]

Abstract: Atherosclerosis is a long-term inflammatory disease of the arterial wall. Increased expression of the cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) is associated with increased proliferation of vascular smooth muscle cells (VSMCs), leading to increased neointima or atherosclerotic lesion formation. Therefore, the functional inhibition of adhesion molecules could be a critical therapeutic target of inflammatory disease. In the present study, we investigate the effect of sulforaphane on the expression of VCAM-1 induced by TNF-α in cultured mouse vascular smooth muscle cell lines. Pretreatment of VSMCs for 2h with sulforaphane (1–5μg/ml) dose-dependently inhibited TNF-α-induced adhesion of THP-1 monocytic cells and protein expression of VCAM-1. Sulforaphane also suppressed TNF-α-induced production of intracellular reactive oxygen species (ROS) and activation of p38, ERK and JNK. Furthermore, sulforaphane inhibited NK-κB and AP-1 activation induced by TNF-α. Sulforaphane inhibited TNF-α-induced ΙκΒ kinase activation, subsequent degradation of ΙκΒα and nuclear translocation of p65 NF-κB and decreased c-Jun and c-Fos protein level. This study suggests that sulforaphane inhibits the adhesive capacity of VSMC and downregulates the TNF-α-mediated induction of VCAM-1 in VSMC by inhibiting the MAPK, NF-κB and AP-1 signaling pathways and intracellular ROS production. Thus, sulforaphane may have beneficial effects to suppress inflammation within the atherosclerotic lesion. [Copyright &y& Elsevier]

Abstract: Carbon monoxide (CO) abrogates TNF-α-mediated inflammatory responses in endothelial cells, yet the underlying mechanism thereof is still elusive. We have previously shown that the anti-inflammatory effect of CO-releasing molecule-3 (CORM-3) is not completely mediated via deactivation of the NF-κB pathway. In this study, we sought to explore other potential mechanisms by which CORM-3 downregulates VCAM-1 expression on TNF-α-stimulated HUVECs. By genome-wide gene expression profiling and pathway analysis we studied the relevance of particular pathways for the anti-inflammatory effect of CORM-3. In CORM-3-stimulated HUVECs significant changes in expression were found for genes implicated in the proteasome and porphyrin pathways. Although proteasome activities were increased by CORM-3, proteasome inhibitors did not abolish the effect of CORM-3. Likewise, heme oxygenase-1 inhibitors did not abrogate the ability of CORM-3 to downregulate VCAM-1 expression. Interestingly, CORM-3 inhibited MAPK p38, and the p38 inhibitor SB203580 downregulated VCAM-1 expression. However, downregulation of VCAM-1 by CORM-3 occurred only at concentrations that partly inhibit ATP production and sodium azide and oligomycin paralleled the effect of CORM-3 in this regard. Our results indicate that CORM-3-induced downregulation of VCAM-1 is mediated via p38 inhibition and mitochondrial respiration, whereas the ubiquitin–proteasome system seems not to be involved. [Copyright &y& Elsevier]

Considering the high prevalence of congenital hypothyroidism (CH) in Isfahan, the possible involvement of endothelial dysfunction in the pathogenesis of CH and the lack of studies in this field, the aim of this study was to determine the endothelial function in CH patients. Methods: During this case-control study, the endothelial function in CH neonates and in those with normal screening results was evaluated during a CH screening program in Isfahan. Peripheral blood samples were obtained for measurement of the von Willebrand factor (vWf), and intercellular and vascular cell adhesion molecule (ICAM and VCAM). In CH patients these biomarkers were measured twice: before and 4 weeks after treatment. Results: In this study, 56 neonates were evaluated: 30 of them were neonates with normal screening results and 26 were diagnosed with CH and classified into two groups according to their TSH levels. The mean ICAM and VCAM were higher in CH patients than in the control group (p < 0.05). The mean ICAM and VCAM decreased significantly after treatment in CH patients (p < 0.05). There is no significant relationship between TSH, ICAM, VCAM and vWf (p > 0.05). Conclusion: The findings of this study demonstrate the possible involvement of the endothelial system in the pathogenesis of CH and its cardiovascular complications. Further studies with a larger sample size and with the measurement of other endothelial function markers are needed. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Inclusion of biophenols in traditional foods transforms them into functional foods that may help to decrease CVD risk. The aim of the present study was to determine whether the consumption of hydroxytyrosol-enriched sunflower oil (HSO) improves certain CVD biomarker values. A total of twenty-two healthy volunteers participated in a cross-over study involving two 3-week periods, separated by a 2-week washout period, in which volunteers consumed 10–15 g/d of either HSO (45–50 mg/d of hydroxytyrosol) or non-enriched (control) sunflower oil. Total cholesterol, LDL-cholesterol, HDL-cholesterol, arylesterase activity, oxidised LDL and soluble vascular cell adhesion molecule (sVCAM-1) levels were measured in the plasma obtained at the beginning and at the end of each treatment period. The HSO group displayed a significantly higher level (P < 0·01) of arylesterase activity and significantly lower levels of oxidised LDL and sVCAM-1 (both P < 0·05) than the control group. These results suggest that HSO may help prevent CVD. [ABSTRACT FROM PUBLISHER]

Lewis DF., Canzoneri BJ., Gu Y, Zhao S, Wang Y. Maternal Levels of Prostacyclin, Thromboxane, ICAM, and VCAM in normal and preeclamptic pregnancies. Am J Reprod Immunol 2010; 64: 376-383 To evaluate whether impaired endothelial function and endothelial inflammatory response occur in parallel in the women with preeclampsia. Venous blood was drawn from normal ( n = 40) and severe preeclamptic (sPE) ( n = 40) pregnant women when they were admitted to the L&D Unit and 24 hrs after delivery. Plasma and serum samples were extracted and measured for 6-keto PGF1α and TXB (stable metabolites of PGI2 and TXA2), and intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) by ELISA. Data are analyzed by Mann-Whitney test and paired t-test. The statistical significance is set as P < 0.05. Plasma 6-keto PGF1α levels were significantly reduced at admission and 24 hr after delivery in sPE compared to normal pregnant controls, P < 0.01. The ratio of 6-keto PGF1α and TXB was significant less in sPE than that in normal pregnant controls before delivery. There was no significant difference for ICAM and VCAM levels between normal and patients with sPE before and after delivery. Maternal 6-keto PGF1α levels and the ratio of 6-keto PGF1α and TXB were decreased in patients with sPE compared to normal pregnant controls. In contrast, maternal ICAM and VCAM levels were not different between the two groups. These data suggest that serum ICAM and VCAM levels may not be sensitive inflammatory biomarkers for preeclampsia. [ABSTRACT FROM AUTHOR]

Background/Aims: This study was conducted to evaluate the anti-inflammatory mechanisms of Erigeron canadensis (EC) on the tumor necrosis factor-α (TNF-α)-, interleukin (IL)-4- and IL-1β-induced stimulation of A549 cells. Methods: In the present study, the anti-inflammatory effects of EC on TNF-α-, IL-4- and IL-1β-induced A549 cells were determined by analyzing eotaxin secretion using ELISA. In addition, the effects of ECon gene expression profiles in stimulated A549 cells were evaluated by microarray analysis. Results: Oligonucleotide microarray analysis revealed that inflammatory-related genes such as NOS1, NOS2A, IL-1β, IL-8 and CSF2 and cell adhesion-related genes such as SELE, MMP3, VCAM1, ICAM1, ITGA7 and ITGB2 were downregulated in EC-treated A549 cells that had been pretreated with TNF-α, IL-4 and IL-1β. In addition, significant decreases in Eotaxin, ICAM, VCAM and IL-8 gene expression were observed in EC-treated A549 cells. Conclusions: EC has an anti-inflammatory effect in stimulated A549 cells. Microarray-based genomic survey is a high-throughput approach that is suitable for the evaluation of gene expression in cell lines that have been treated with EC. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: Pregnancy-associated plasma protein-A (PAPP-A), a metalloproteinase that serves to modulate local insulin-like growth factor (IGF) action, is upregulated in atherosclerotic plaque. However, little is known about the cellular mechanisms underlying this elevated PAPP-A. Objective: To continue study of PAPP-A expression and its regulation in human vascular cells, with a focus on endothelial cells. Design: Primary cultures of human coronary artery endothelial cells (ECs) were treated without and with cytokines, growth factors, or low density lipoprotein (LDL). PAPP-A mRNA, protein, and protease activity were assessed using real-time PCR, ultra-sensitive PAPP-A ELISA and cell-free proteolysis of IGF binding protein (IGFBP-4), respectively. In addition, vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), monocyte chemotactic protein (MCP-1), IGF-I, IGF-I receptor, and IGFBP-4 and -5 mRNA expression levels were determined. Results: ECs in culture show little basal PAPP-A expression. The pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-β, stimulated PAPP-A expression (TNF-α≫IL-1β), whereas there was no effect of IL-6, transforming growth factor-β, IGF-I, insulin, fibroblast growth factor or epidermal growth factor in these cells. Stimulation of PAPP-A expression by TNF-α was associated with significantly increased VCAM, ICAM, and MCP-1 expression but without major changes in other IGF system components. TNF-α-induced VCAM, ICAM, and MCP-1 expression (⩽4h) preceded PAPP-A expression (24h). The anti-oxidant, N-acetyl cysteine, inhibited TNF-α-induced PAPP-A expression without altering the induction in VCAM, ICAM, and MCP-1. Treatment with native or oxidized LDL had no effect on PAPP-A expression in ECs. Comparative results in human coronary smooth muscle cells indicated qualitative and quantitative differences in PAPP-A expression and regulation between the two vascular cell types. Conclusions: Human coronary artery ECs express PAPP-A mRNA and functional protein when activated by the pro-inflammatory cytokine, TNF-α. This study complements work on PAPP-A expression in human coronary artery SMCs and human monocyte-derived macrophages and suggests an interactive model of PAPP-A regulation and action in human atherosclerotic plaque. [Copyright &y& Elsevier]

Hyperaldosteronism is associated with hypertension, cardiovascular fibrosis, and electrolyte disturbances, including hypomagnesemia. Mechanisms underlying aldosterone-mediated Mg(2+) changes are unclear, but the novel Mg(2+) transporters TRPM6 and TRPM7 may be important. We examined whether aldosterone influences renal TRPM6/7 and the TRPM7 downstream target annexin-1 and tested the hypothesis that Mg(2+) administration ameliorates aldosterone-induced cardiovascular and renal injury and prevents aldosterone-associated hypertension. C57B6 mice were studied (12 weeks, n=8 to 9/group); (1) control group (0.2% dietary Mg(2+)), (2) Mg(2+) group (0.75% dietary Mg(2+)), (3) aldosterone group (Aldo, 400 microg/kg/min and 0.9% NaCl drinking water), and (4) Aldo+Mg(2+) group. Blood pressure was unaltered by aldosterone and was similar in all groups throughout the experiment. Serum Na(+) was increased and serum K(+) and Mg(2+) decreased in the Aldo group. Aldo mice had hypomagnesuria and proteinuria, and renal, cardiac, and aortic fibrosis, which were normalized by Mg(2+) supplementation. Renal and cardiovascular expression of interleukin-6, VCAM1 and COX2 was increased in the Aldo group. Magnesium attenuated renal and cardiac interleukin-6 content and decreased renal VCAM1 and cardiac COX2 expression (P<0.05). Aldosterone decreased expression of renal TRPM7 and the downstream target annexin-1 (P<0.05) without effect on TRPM6. Whereas Mg(2+) increased mRNA expression of TRPM6 and TRPM7, it had no effect on TRPM7 and annexin-1 protein content. Our data demonstrate that aldosterone mediates blood pressure-independent renal and cardiovascular fibrosis and inflammation through Mg(2+)-sensitive pathways. We suggest that altered Mg(2+) metabolism in hyperaldosteronism may relate to TRPM7 downregulation and that Mg(2+) protects against cardiovascular and renal damaging actions of aldosterone. [ABSTRACT FROM AUTHOR]

Adipocytokines involved in inflammation and the acute phase responders have been found to be increased in the metabolic syndrome (MS). The aim of the study was to compare the 'normal' weight women's fibrinogen, hsCRP, adiponectin, TNF-α, vascular cell adhesion molecule (VCAM) with obese patients with MS, and to evaluate the association between fibrinogen, hsCRP, adiponectin, TNF-αα, VCAM and insulin resistance. The study included 52 obese women who met the criteria for MS defined as in 2001, the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) ATP III and 24 normal women. Serum concentrations of glucose (FBG), triglyceride, total and HDL-Cholesterol were determined by enzymatic procedures, serum insulin was measured by chemiluminescence, plasma levels of adiponectin, TNF-α and VCAM by Elisa, hsCRP by immunoturbimetric assay and fibrinogen by coagulation method. Measurements of insulin resistance were obtained using the homeostasis model assessment. Mean plasma levels of adiponectin, TNF-α, VCAM, fibrinogen and hsCRP were found 6.11±2.39 mg/ml, 3.10±3.30 pg/ml, 14.21±4.00 ng/ml, 375.49±49.67 mg/dl, 0.33±0.10 mg/dl in the obese with MS; 6.20±2.48 mg/ml, 3.01±1.68 pg/ml, 12.63±2.54 ng/ml, 304.06±49.52 mg/dl, 0.30±0.19 mg/dl in the normal women, respectively. Mean fasting insulin level and HOMA-IR were measured 13.80±6.32 mU/ml and 3.69±1.90 mU/ml, respectively in obese with MS. In normal women, fasting insulin level and HOMA-IR were measured 8.30±3.08 mU/ml and 1.49±0.37, respectively. Mean levels of adiponectin were positively correlated with mean TNF-α levels in the obese with MS (r=0.472, p=0.001). VCAM was negatively correlated with TNF-α levels (r=-0.301, p=0.038) in the obese with MS. This study demonstrated that TNF-α showed a positive association with adiponectin and a negative association with VCAM in the obese women with MS. [ABSTRACT FROM AUTHOR]

Early-onset type 2 diabetes (T2DM) may lead to very early vascular complications. Cardiovascular mortality is two to five times higher in adults with diabetes than in people without diabetes. The cardiovascular risk of young people with T2DM is unknown. T2DM in young people is associated with marked visceral obesity, insulin resistance and microalbuminuria. We recently showed that these subjects did not improve in either fitness (maximum volume of oxygen consumption, VO2max) or glucose disposal after exercise training.Seven subjects with early-onset T2DM (aged 26.1±0.9 years, body mass index [BMI] 35.6±1.2 kg/m2) and 14 age-matched obese subjects with normal glucose tolerance (aged 25. 6±0.9 years, BMI 34. 3±1.4 kg/m2) underwent aerobic training for 12 weeks. Serum vascular inflammatory markers (high-sensitivity C-reactive protein [hsCRP], soluble intercellular adhesion molecule [sICAM-1], soluble vascular cell adhesion molecule [sVCAM-1], E-Selectin and P-Selectin) were measured before and after the training programme.At baseline, plasma concentrations of vascular inflammatory markers were significantly elevated in both groups. They did not improve after exercise. [ABSTRACT FROM PUBLISHER]

Increasing evidence indicates that replicative senescence and premature endothelial senescence could contribute to endothelial dysfunction. This study aims at testing the hypothesis that a high-fat diet may lead to premature vascular endothelial senescence in a nonhuman primate model. We isolated endothelial cells from left and right femoral arteries in 10 baboons before and after a 7-wk high-fat dietary treatment. We compared the morphological alterations, replicative capacities, and senescence-associated β-galactosidase activities (SA-β-gal) at these two time points. We found that high-fat diet increased the prevalence of endothelial senescence. Endothelial replicative capacities declined dramatically, and SA-β-gal activities increased significantly in postdietary challenge. There was no change in telomeric length using quantitative flow fluorescence in situ hybridization analysis, suggesting that some stressors lead to cell senescence independent of telomere dysfunction. Our findings that high-fat diet causes endothelial damage through the premature senescence suggest a novel mechanism for the diet-induced endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Activation of vascular endothelium plays an essential role in vasoocclusion in sickle cell disease. The anti-inflammatory agents dexamethasone and adhesion molecule-blocking antibodies were used to inhibit endothelial cell activation and hypoxia-induced vasoocclusion. Transgenic sickle mice, expressing human α-, βS-, and βS-Antilles-globins, had an activated vascular endothelium in their liver, lungs, and skin, as exhibited by increased activation of NF-κB compared with normal mice. NF-κB activation increased further in the liver and skin after sickle mice were exposed to hypoxia. Sickle mice had decreases in red blood cell (RBC) velocities and developed vasoocclusions in subcutaneous venules in response to hypoxia. Dexamethasone pretreatment prevented decreases in RBC velocities and inhibited vasoocclusions and leukocyte-endothelium interactions in venules after hypoxia. Dexamethasone treatment inhibited NF-κB, VCAM-1, and ICAM-1 expression in the liver, lungs, and skin of sickle mice after hypoxia-reoxygenation. VCAM-1 or ICAM-1 blockade with monoclonal antibodies mimicked dexamethasone by inhibiting vasoocclusion and leukocyte adhesion in sickle mice, demonstrating that endothelial cell activation and VCAM-1 and ICAM-1 expression are necessary for hypoxia-induced vasoocclusion in sickle mice. VCAM-1, ICAM-1, and vasoocclusion increased significantly 3 days after dexamethasone discontinuation, possibly explaining rebounds in vasoocclusive crises observed after withdrawal of glucocorticosteroids in sickle patients. We conclude that anti-inflammatory treatments that inhibit endothelial cell activation and adhesion molecule expression can inhibit vasoocclusion in sickle cell disease. Rebounds in vasoocclusive crises after dexamethasone withdrawal are caused by rebounds in endothelial cell activation. [ABSTRACT FROM AUTHOR]