Vascular Cell Adhesion Molecule Type Research Articles

Resistin Enhances VCAM-1 Expression and Monocyte Adhesion in Human Osteoarthritis Synovial Fibroblasts by Inhibiting MiR-381 Expression through the PKC, p38, and JNK Signaling Pathways

The development of osteoarthritis (OA) is characterized by synovial inflammation and the upregulation of vascular cell adhesion molecule type 1 (VCAM-1) in human osteoarthritis synovial fibroblasts (OASFs). This increase in VCAM-1 expression promotes monocyte adhesion to OASFs. The adipokine resistin is known to promote the release of inflammatory cytokines during OA progression. In this study, we identified significantly higher levels of resistin and CD68 (a monocyte surface marker) expression in human OA tissue compared with in healthy control tissue. We also found that resistin enhances VCAM-1 expression in human OASFs and facilitates the adhesion of monocytes to OASFs. These effects were attenuated by inhibitors of PKCα, p38, and JNK; their respective siRNAs; and by a microRNA-381 (miR-381) mimic. In our anterior cruciate ligament transection (ACLT) rat model of OA, the inhibition of resistin activity prevented ACLT-induced damage to the OA rat cartilage and pathological changes in resistin and monocyte expression. We also found that resistin affects VCAM-1 expression and monocyte adhesion in human OASFs by inhibiting miR-381 synthesis via the PKCα, p38, and JNK signaling pathways. Our clarification of the crucial role played by resistin in the pathogenesis of OA may lead to more effective therapy that reduces OA inflammation.

Effects of soy isoflavones on serum systemic and vascular inflammation markers and oxidative stress in peritoneal dialysis patients: A randomized controlled trial.

Cardiovascular disease (CVD) is common in peritoneal dialysis (PD) patients. This study was designed to investigate the effects of isoflavones on systemic and vascular inflammation markers and oxidative stress in PD patients. In this randomized clinical trial, 40 PD patients were randomly assigned to either the isoflavone or the placebo group. The isoflavone group received 100 mg soy isoflavones daily for 8 weeks, whereas the placebo group received corresponding placebos. At baseline and the end of eighth week, serum high sensitive C-reactive protein (hs-CRP), intercellular adhesion molecule type 1 (ICAM-1), vascular cell adhesion molecule type 1 (VCAM-1), E-selectin, and malondialdehyde were measured. Serum VCAM-1 decreased significantly in the isoflavone group at the end of Week 8 compared to baseline (p = .01), whereas no significant change was observed in the placebo group. Serum ICAM-1 decreased significantly in the isoflavone (p = .01) and placebo (p = .01) group compared to baseline. However, the reduction of ICAM-1 was significantly higher in the isoflavone group than in the placebo group (p = .02). There were no significant differences between the two groups in mean changes of serum E-selectin, malondialdehyde, and hs-CRP. This study indicates that isoflavones reduce serum VCAM-1 and ICAM-1, which are two CVD risk factors, in PD patients.

Effect of Synbiotic and Probiotic Supplementation on Serum Levels of Endothelial Cell Adhesion Molecules in Hemodialysis Patients: a Randomized Control Study.

The aim of this study was to investigate the effect of synbiotic and probiotic supplementation on serum vascular dysfunction and necrosis markers in hemodialysis (HD) patients. In this randomized, double-blind, placebo-controlled trial, 75 HD patients were randomly assigned to either the synbiotic or probiotic or placebo group. The patients in the synbiotic group received 15g of prebiotics and 5g probiotic powder containing Lactobacillus acidophilus strain T16 (IBRC-M10785), Bifidobacterium bifidum strain BIA-6, Bifidobacterium lactis strain BIA-6, Bifidobacterium longum strain LAF-5 (2.7 × 107CFU/g each) in sachets (n = 25), whereas the probiotic group received 5g probiotics same to the first group with 15g of maltodextrin powder in sachets (n = 25) and the placebo group received 20g of maltodextrin powder in sachets (n = 25) for 12weeks. At baseline and the end of the study, serum concentrations of soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), cytokeratin 18 (CK-18) as the necrosis marker, uric acid, and phosphate levels were measured. Feces also were collected for microbiota colony counting. Serum ICAM-1 level reduced significantly in the synbiotic group after the intervention period (P = 0.02), and this reduction was significantly different in the synbiotic group in comparison to the placebo group (P = 0.03). Serum levels of VCAM-1 and CK-18 were not significantly different between the groups. However, the reduction in serum levels of VCAM-1 in the synbiotic group was significantly higher in comparison to the placebo group (P = 0.01). Multivariate linear regression analysis revealed that ∆ phosphate was the sole independent determinant of ∆ICAM-1 (P = 0 < 001). The study indicated that synbiotic supplementation reduced serum ICAM-1 level, which is a risk factor for cardiovascular diseases in HD patients, but has no effect on the necrosis marker. Trial registration: www.irct.ir (IRCT2017041233393N1).

Diagnostic and prognostic value of assessment of soluble adhesion molecules sICAM-1 and sVCAM-1 in septic patients

The review is devoted to the assessment of use of cell adhesion molecules including intercellular adhesion molecule type 1 (ICAM-1) and vascular cell adhesion molecule type 1 (VCAM-1) as additional laboratory markers for severity assessment and as predictors of outcome in septic patients. One of the very important pathogenetic components of this state is known to be endothelium activation replaced by its dysfunction. The level of expression of these molecules on endothelial cell membrane affects leukocyte migration from the vessels to surrounding tissues. Besides, a number of cell adhesion molecules are expressed on immunocompetent cells that influences the development of immune response (both innate and acquired). The main characteristics of ICAM-1 and VCAM-1 are presented, including the possibility of soluble forms formation (sICAM-1, sVCAM-1) due to shedding of cell membrane induced by proteolytic enzymes. The results of literature analysis demonstrate that in sepsis the serum content of sICAM-1 and sVCAM-1 is significantly higher than in healthy subjects. In most cases their level is higher than in patients with other critical states (such as severe infectious inflammatory processes, myocardial infarction, stroke, burns, etc.) that according to some authors allows their using for differential diagnosis of sepsis and other critical states. There is no consensus on correlation with disease severity (sepsis, severe sepsis, septic shock), presence of multiple organ failure and its prediction, and lethal outcomes. Results inconsistency most probably can be explained by differences in study design. Nevertheless, continuing studies in this direction is considered perspective.

Pomegranate Juice Increases Sirtuin1 Protein in Peripheral Blood Mononuclear Cell from Patients with Type 2 Diabetes: A Randomized Placebo Controlled Clinical Trial.

Few studies have examined anti-inflammatory effects of pomegranate juice (PJ). The present study aimed to evaluate the effect of PJ on nuclear factor kappa B (NF-κB) p65 and sirtuin1 in peripheral blood mononuclear cell (PBMC), and plasma vascular inflammation biomarkers. Patients with type 2 diabetes were randomly assigned to either the PJ (n = 22) or the placebo group (n = 22). The patients in the PJ group received 250 mL of PJ daily for 12 weeks, whereas the placebo group received corresponding control beverages of similar color and energy content. At baseline and at the end of week 12, fasting plasma concentrations of soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), and soluble E-selectin (sE-selectin) were measured. NF-κB p65 and SIRT1 were measured in the PBMC. Plasma sE-selectin concentration decreased significantly in the PJ group at the end of week 12 compared to baseline (P < 0.001 for treatment effect), and the reduction was significant in comparison with the placebo group (P < 0.05 for treatment effect). There were no significant differences between the two groups in plasma sICAM-1 and sVCAM-1. At the end of the study, compared with the placebo group, NF-κB p65 in PBMC was significantly lower (P < 0.01 for treatment effect) and SIRT1 was significantly higher (P < 0.0001 for treatment effect) in the PJ group. This study supports the PJ consumption as a food with potential benefits in individuals with type 2 diabetes as evidenced by improvements in NF-κB and SIRT1 levels in PBMC of study participants.

Взаємозвʼязок між коефіцієнтом атерогенності та рівнем розчинної форми молекули адгезії судинного ендотелію 1 типу в осіб з артеріальною гіпертензією і цукровим діабетом 2 типу

Взаємозвʼязок між коефіцієнтом атерогенності та рівнем розчинної форми молекули адгезії судинного ендотелію 1 типу в осіб з артеріальною гіпертензією і цукровим діабетом 2 типу

Serum proteins mediate depression's association with dementia.

The latent variable “δ” (for “dementia”) uniquely explains dementia severity. Depressive symptoms are independent predictors of δ. We explored 115 serum proteins as potential causal mediators of the effect of depressive symptoms on δ in a large, ethnically diverse, longitudinal cohort. All models were adjusted for age, apolipoprotein E, education, ethnicity, gender, hemoglobin A1c, and homocysteine, and replicated in randomly selected 50% subsets. Alpha1-antitrypsin (A1AT), FAS, Heparin-binding EGF-like Growth Factor (HB-EGF), Insulin-like Growth Factor-1 (IGF-1), Luteinizing Hormone (LH), Macrophage Inflammatory Protein type 1 alpha (MIP-1α), Resitin, S100b, Tissue Inhibitor of Metalloproteinase type 1 (TIMP-1), and Vascular Cell Adhesion Molecule type 1 (VCAM-1) each were partial mediators of depression’s association with δ. These proteins may offer targets for the treatment of depression’s specific effect on dementia severity and Alzheimer’s Disease (AD) conversion risk.

Simvastatin Attenuates Endothelial Activation through 15-Epi-Lipoxin A4 Production in Murine Chronic Chagas Cardiomyopathy.

Current treatments for chronic Chagas cardiomyopathy, a disease with high mortality rates and caused by the protozoan Trypanosoma cruzi, are unsatisfactory. Myocardial inflammation, including endothelial activation, is responsible for the structural and functional damage seen in the chronic phase. The clinical efficacy of benznidazole could be improved by decreasing chronic inflammation. Statins, which have anti-inflammatory properties, may improve the action of benznidazole. Here, the action of simvastatin in a murine model of chronic Chagas cardiomyopathy and the link with the production of the proresolving eicosanoid 15-epi-lipoxin A4, produced by 5-lipoxygenase, are evaluated. Simvastatin decreased the expression of the adhesion molecules E-selectin, intracellular adhesion molecule type 1 (ICAM-1), and vascular cell adhesion molecule type 1 (VCAM-1) in T. cruzi-infected mice. However, when this drug was administered to 5-lipoxygenase-deficient mice, the anti-inflammatory effect was not observed unless exogenous 15-epi-lipoxin A4 was administered. Thus, in chronic Chagas disease, 5-epi-lipoxin A4 induced by simvastatin treatment could improve the pathophysiological condition of patients by increasing the trypanocidal action of benznidazole.

CORRELATION OF INFLAMMATION BIOMARKERS WITH THE TRADITIONAL RISK FACTORS IN PATIENTS WITH ACUTE CORONARY SYNDROME

Actuality of cardiovascular diseases today determines the high interest to study pathogenesis of atherosclerosis and to searching new risk factors which could help to optimize primary and secondary prevention. Study the correlation between biomarkers of inflammation and traditional risk factors (TRF) in patients with different forms of ischemic heart disease is really important today. Aim. To determine the correlation between TRF and the level of biomarkers of the inflammation and endothelial dysfunction in patients with acute coronary syndrome (ACS). Material and methods. Patients (n=62) aged from 24 to 50 years (mean age 43.98±4.73), who were admitted to the hospital due to ACS, were included into the study. Correlations between TRF and the levels of biomarkers of the inflammation and endothelial dysfunction were assessed. The following biomarkers levels were determined: high-sensitivity C-reactive protein (hsCRP), homocysteine, soluble vascular cell (sVCAM-1) and intracellular (sICAM-1) adhesion molecule type 1, soluble E-selectin (sE-selectin), nitrate, neopterin, matrix metalloproteinase type 3 (MMP-3). Results. TRF, including modifiable ones, were often revealed in patients of the studied group. Some correlations between TRF and high concentrations of inflammatory biomarkers were determined. Patients with the family history of early cardiovascular diseases had higher concentration of sVCAM-1 (1047.78±516.98 ng/ml) in comparison with the patients without this TRF (705.57±239.28 ng/ml), p=0.017. Patients with arterial hypertension had higher level of MMP-3 (9.31±3.63 ng/ml) versus patients without hypertension (5.02±3.66 ng/ml), р=0.011). Patients with abdominal obesity compared with patients without this TRF demonstrated higher concentration of nitrate in acute (208.45±91.85 ng/ml vs 154.53 ng/ml, р=0.028) and long-term (193.53±40.02 ng/ml vs 173.48 ng/ml, р=0.028) periods of ASC. Conclusion. The study showed the significant correlation between ТRF and high levels of some biomarkers of inflammation and endothelial dysfunctions in patients with ACS. So it is probably associated with more rapid progression of the atherosclerosis, higher risk of atherothrombotic events, complicated course of ischemic heart disease and unfavorable outcomes.

Effects of ginger on serum glucose, advanced glycation end products, and inflammation in peritoneal dialysis patients

ObjectiveThe aim of this study was to investigate the effects of ginger supplementation on serum glucose, advanced glycation end products, oxidative stress, and systemic and vascular inflammatory markers in patients on peritoneal dialysis (PD). MethodsIn this randomized, double-blind, placebo-controlled trial, 36 patients on PD were randomly assigned to either the ginger or the placebo group. The patients in the ginger group received 1000 mg/d ginger for 10 wk, whereas the placebo group received corresponding placebos. At baseline and the end of week 10, serum concentrations of glucose, carboxymethyl lysine, pentosidine, malondialdehyde (MDA), high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), and sE-selectin were measured after a 12- to 14-h fast. ResultsSerum fasting glucose decreased significantly up to 20% in the ginger group at the end of week 10 compared with baseline (P < 0.05), and the reduction was significant in comparison with the placebo group (P < 0.05). There were no significant differences between the two groups in mean changes of serum carboxymethyl lysine, pentosidine, MDA, hs-CRP, sICAM-1, sVCAM-1, and sE-selectin. ConclusionThis study indicated that daily administration of 1000 mg ginger reduces serum fasting glucose, which is a risk factor for hyperinsulinemia, dyslipidemia, peritoneal membrane fibrosis, and cardiovascular disease, in patients on PD.

Association of malnutrition-inflammation score, dialysis-malnutrition score and serum albumin with novel risk factors for cardiovascular diseases in hemodialysis patients

Background: This study was designed to investigate the associations between malnutrition-inflammation score (MIS), dialysis-malnutrition score (DMS) and serum albumin with novel risk factors for cardiovascular diseases (CVD) in hemodialysis (HD) patients. Methods: In this cross-sectional study, 291 HD patients were randomly selected from among 2302 adult HD patients in Tehran HD centers. The MIS and DMS were determined during one of the dialysis sessions in these patients. In addition, 4 mL blood was obtained before dialysis and analyzed for serum albumin and novel risk factors for CVD, including C-reactive protein (CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), sE-selectin, malondialdehyde (MDA), nitric oxide (NO), endothelin-1 and lipoprotein (a) [Lp (a)]. Results: MIS and DMS were significantly positively correlated with serum CRP (p < 0.01) and sICAM-1 (p < 0.01), whereas serum albumin concentration was significantly negatively correlated with serum CRP (p < 0.01) and sICAM-1 (p < 0.01). There were no significant correlations between MIS, DMS and serum albumin with serum concentrations of sVCAM-1, sE-selectin, MDA, NO, endothelin-1 and Lp (a). Conclusion: This study indicates that protein-energy wasting indicators in HD patients are associated with serum CRP and sICAM-1, as two CVD risk factors.

RELATIONSHIP BETWEEN SERUM SOLUBLE CELLULAR ADHESION MOLECULES CONCENTRATION AND CHOLESTEROL AND LIPOPROTEINS IN PATIENTS REFERRED TO ATHEROSCLEROSIS

ObjectivesEvidence is emerging that serum soluble cellular adhesion molecules contributes to the development and progression of atherosclerosis and cardiovascular disease. Little is known, however, regarding an association between soluble cellular...

Effects of Marine Omega-3 Fatty Acids on Serum Systemic and Vascular Inflammation Markers and Oxidative Stress in Hemodialysis Patients

Background and Aims: High concentrations of serum inflammation markers, especially vascular inflammation markers, are an important risk factor for cardiovascular diseases in hemodialysis patients. The present study was designed to investigate the effects of marine omega-3 fatty acids on serum systemic and vascular inflammation markers and oxidative stress in hemodialysis patients. Methods: Thirty-four hemodialysis patients were randomly assigned to either the marine omega-3 fatty acid or the placebo group. Patients in the omega-3 fatty acid group received 2,080 mg marine omega-3 fatty acids daily for 10 weeks, whereas the placebo group received a corresponding placebo.At baseline and the end of week 10, 5 ml blood was collected after a 12- to 14-hour fast. Results: Mean serum soluble intercellular adhesion molecule type 1 (sICAM-1) decreased significantly in the omega-3 fatty acid group at the end of week 10 compared to baseline (p < 0.05) and this reduction was significant in comparison with the placebo group (p < 0.05). No significant differences were observed between the two groups in mean changes in serum soluble vascular cell adhesion molecule type 1, sE-selectin, sP-selectin, C-reactive protein, interleukin-6, tumor necrosis factor-α, malondialdehyde and total antioxidant capacity. Conclusion: The results of the present study indicate that marine omega-3 fatty acids can reduce serum sICAM-1, a risk factor for cardiovascular diseases, but it has no effect on serum systemic inflammation markers and oxidative stress in hemodialysis patients.

Effects of l-carnitine Supplement on Serum Amyloid A and Vascular Inflammation Markers in Hemodialysis Patients: A Randomized Controlled Trial

We studied the effects of l-carnitine supplement on serum amyloid A (SAA), a systemic inflammation marker, and vascular inflammation markers in hemodialysis patients. This was a randomized, double-blind, placebo-controlled trial. The study was performed in Soodeh Hemodialysis Center in Islamshahr, Iran. We included 36 hemodialysis patients (15 men and 21 women). The patients on hemodialysis were randomly assigned to either a carnitine or a placebo group. Patients in the carnitine group received 1,000 mg/day oral l-carnitine for 12 weeks, whereas patients in the placebo group received a corresponding placebo during the study. Serum free carnitine, SAA, soluble intercellular adhesion molecule type 1, soluble intercellular adhesion molecule type 2, soluble vascular cell adhesion molecule type 1, sE-selectin, sP-selectin, and oxidized low-density lipoprotein were measured at baseline and at the end of week 12 of the study. Mean serum free carnitine concentration increased significantly to 150% of baseline in the carnitine group at the end of week 12 (P < .001), whereas serum SAA showed a significant 32% decrease (P < .001). No significant changes were observed in the serum concentrations of free carnitine and SAA in the placebo group during the study. There were no significant differences between the two groups in mean changes in serum soluble intercellular adhesion molecule type 1, soluble intercellular adhesion molecule type 2, soluble vascular cell adhesion molecule type 1, sE-selectin, sP-selectin, and oxidized low-density lipoprotein concentrations. The study indicates that l-carnitine supplement reduces serum SAA, which is a risk factor for cardiovascular diseases in hemodialysis patients, but has no effect on vascular inflammation markers.

α4 Integrin/FN-CS1 mediated leukocyte adhesion to brain microvascular endothelial cells under flow conditions

Insights into sequential leukocyte–endothelial interactions during leukocyte trafficking have been obtained through experiments using human umbilical vein endothelial cells (HUVEC) under flow conditions. To investigate leukocyte–brain endothelial cell interactions, we developed a dynamic in vitro system, using Transfected Human Brain Microvascular Endothelial Cells (THBMEC) and a parallel plate flow chamber. Human peripheral blood mononuclear cells (PBMC) were perfused across confluent THBMEC cultures at a velocity that approximates the rate found in human brain capillaries. Leukocyte–THBMEC interactions were visualized by phase-contrast microscopy, and images were captured on a CCD camera. To simulate inflammatory conditions, we activated THBMEC with the inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), which up-regulated chemokine and adhesion molecule expression in THBMEC without affecting the distribution of immunoreactivity for tight junction-associated proteins. PBMC adhesion was enhanced by cytokine-mediated activation of THBMEC. G protein-coupled receptor (GPCR) activation was essential for leukocyte–THBMEC interaction, as pertussis toxin (PTX) treatment of PBMC abrogated PBMC adhesion to activated THBMEC. The anti-α4 integrin antibody, natalizumab, infused into MS patients, significantly reduced the adhesion of their ex vivo PBMC to activated THBMEC under flow conditions. Further study showed that alternatively spliced fibronectin containing the CS1 region (FN-CS1), but not Vascular Cell Adhesion Molecule type 1 (VCAM-1), was the ligand of α4 integrin on activated THBMEC. Blocking FN-CS1 abrogated PBMC adhesion on activated THBMEC, while anti-VCAM-1 antibodies had no effect. These results established a novel in vitro dynamic BBB model. We also demonstrated the dependence of leukocyte–endothelial interactions in this model on α4 integrins and FN-CS1.

Role of inflammatory markers in brain ischemia

Inflammatory mechanisms play an important role in the risk of stroke and during the acute phase of brain ischemia, which contributes to functional outcome of patients. We review the role of inflammatory markers in these aspects of brain ischemia. Systemic inflammatory mechanisms are associated with higher risk of stroke and vascular recurrences after a first ischemic stroke. Several inflammatory molecules are implicated during the acute phase of ischemic stroke, such as cytokines (interleukin-6, tumor necrosis factor-alpha), adhesion cell molecules (vascular cell adhesion molecule type 1, intercellular adhesion molecule type 1) and metalloproteinases. Metalloproteinases and vascular cell adhesion molecule levels are useful in the diagnosis of ischemic stroke. Inflammatory cytokines (interleukin-6 and tumor necrosis factor-alpha) and adhesion cell molecules are related to the presence of early neurological deterioration and infarct volume. Finally, metalloproteinases play an important role in the development of hemorrhagic transformation. Molecular markers of inflammation can be useful tools for the management of patients with ischemic stroke, both during the acute phase and to predict prognosis and prevent the risk of a new vascular event.

Tu-P7:105 Selected markers of inflammation, past chlamydia pneumoniae infection in patients with stable angina pectoris, without traditional risk factors

The aim of this study was to investigate the effects of ginger supplementation on serum glucose, advanced glycation end products, oxidative stress, and systemic and vascular inflammatory markers in patients on peritoneal dialysis (PD).In this randomized, double-blind, placebo-controlled trial, 36 patients on PD were randomly assigned to either the ginger or the placebo group. The patients in the ginger group received 1000 mg/d ginger for 10 wk, whereas the placebo group received corresponding placebos. At baseline and the end of week 10, serum concentrations of glucose, carboxymethyl lysine, pentosidine, malondialdehyde (MDA), high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), and sE-selectin were measured after a 12- to 14-h fast.Serum fasting glucose decreased significantly up to 20% in the ginger group at the end of week 10 compared with baseline (P < 0.05), and the reduction was significant in comparison with the placebo group (P < 0.05). There were no significant differences between the two groups in mean changes of serum carboxymethyl lysine, pentosidine, MDA, hs-CRP, sICAM-1, sVCAM-1, and sE-selectin.This study indicated that daily administration of 1000 mg ginger reduces serum fasting glucose, which is a risk factor for hyperinsulinemia, dyslipidemia, peritoneal membrane fibrosis, and cardiovascular disease, in patients on PD.

Effect of Intensive Glycemic Control on Levels of Markers of Inflammation in Type 1 Diabetes Mellitus in the Diabetes Control and Complications Trial

Type 1 diabetes mellitus is associated with an increased risk of cardiovascular disease (CVD) that is not fully explained by conventional risk factors. The Diabetes Control and Complications Trial (DCCT) showed that intensive diabetes therapy reduced levels of LDL cholesterol and triglycerides but increased the risk of major weight gain, which might adversely affect CVD risk. The present study examined the effect of intensive therapy on levels of several markers of inflammation that have been linked to risk of CVD. We measured levels of inflammatory biomarkers in stored baseline and 3-year follow-up serum specimens from a random sample of 385 participants in the DCCT, a multicenter trial in which 1441 subjects aged 13 to 39 years with type 1 diabetes mellitus were randomized to intensive or conventional diabetes treatment. The markers included high-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), and the 55-kDa soluble tumor necrosis factor-alpha receptor 1 (sTNF-R1). We examined the effect of intensive therapy on the change in levels of the inflammatory markers. In unadjusted analyses, levels of hsCRP and sTNF-R1 increased in both treatment groups after 3 years of follow-up, with no significant difference between groups for hsCRP (P=0.53) but with a greater increase of sTNF-R1 in the intensive therapy group (P=0.002). In contrast, mean levels of sICAM-1 and sVCAM-1 decreased among participants assigned to intensive therapy, whereas they did not change among those in the conventional treatment group (P=0.03 for sICAM-1; P=0.03 for sVCAM-1). After adjustment for baseline levels and other factors, intensive therapy remained associated with a significant decrease in sICAM-1 (P=0.02) and an increase in sTNF-R1 (P=0.03). For hsCRP, there was a significant interaction between the top third of weight gain and treatment assignment (P=0.03). In subgroup analyses among subjects undergoing intensive therapy, hsCRP levels increased among those who gained the most weight, whereas it decreased among those in the bottom third of weight gain (P=0.0004). Intensive therapy in patients with type 1 diabetes mellitus reduced levels of sICAM-1 and increased levels of sTNF-R1 and of hsCRP among those who gained weight. These data demonstrate that the effect of intensive therapy on inflammation is complex and, to the extent that hsCRP is a risk factor, suggest that the risk of atherosclerosis among diabetic patients may be influenced by the degree of weight gain while undergoing intensive therapy.

Evaluation of markers of endothelial damage in cases of young myocardial infarction

The pathogenesis of arterial thrombotic disease involves multiple genetic and environmental factors related to atherosclerosis and thrombosis. The endothelium is a monolayer of polygonal cells that extend continuously over the luminal surface of the entire vasculature. Injury to the endothelium leads to dysfunction. The causes of injury include lipids, immune complexes, microorganisms, smoking, hypertension, aging, diabetes mellitus and trauma. Studies have been done to evaluate the role of different adhesion molecules on the endothelial membrane in the pathogenesis of atherosclerosis. These molecules are intercellular adhesion molecule type-1 (ICAM-1), vascular cell adhesion molecule type-1 (VCAM-1), platelet/endothelial cell adhesion molecule-1 (PECAM-1), soluble P-selectin (sP-selectin) and soluble E-selectin (sE-selectin). One-hundred and twenty patients of myocardial infarction (age below 40 years) were recruited from the out-patients department of Department of Cardiology, KEM Hospital, Mumbai. All the patients were recruited 8–10 weeks after stabilization after MI. We estimated the levels of sP-selectin, sE-selectin, sPECAM-1 and serum homocysteine. Healthy age and sex-matched controls and family controls were also recruited in the present study. The levels of sP-selectin, sE-selectin and sPECAM-1 did not differ significantly in cases as compared to controls ( p > 0.05). Hyperhomocysteinemia was significantly associated with MI in comparison with controls ( p < 0.001) with an odds ratio of 6.26 (95% confidence limits 3.11–12.76). Folic acid was able to correct hyperhomocysteinemia in a large majority of the cases. Although the levels of sP-selectin, sE-selectin and sPECAM-1 decreased after folic acid therapy, it was only sE-selectin which was significantly reduced ( p < 0.05). Thus, folic acid had a dual effect in that it reduced hyperhomocysteinemia and sE-selectin which showed a significant reduction on folate supplementation for 15 days.

Levels of Soluble Adhesion Molecules Are Elevated in the Cerebrospinal Fluid of Children with Moyamoya Syndrome

The pathogenesis of moyamoya syndrome is unknown; however, previous studies suggested an inflammatory component. Because adhesion molecules mediate inflammation during cerebral ischemia, we measured the levels of soluble isoforms of the endothelial adhesion molecules vascular cell adhesion molecule Type 1, intercellular adhesion molecule Type 1, and E-selectin in serum and cerebrospinal fluid (CSF) samples from children with moyamoya syndrome. Serum and CSF samples were obtained from children with moyamoya syndrome (n = 20) and patients with congenital spinal deformities (n = 20). Soluble vascular cell adhesion molecule Type 1, intercellular adhesion molecule Type 1, and E-selectin levels were measured in enzyme-linked immunoassays. The correlation between the levels of soluble adhesion molecules and the Suzuki angiographic classification was analyzed. CSF/serum albumin index values were also measured, to determine the integrity of the blood-brain barrier. Compared with the control group, children with moyamoya syndrome exhibited significantly elevated CSF levels of soluble vascular cell adhesion molecule Type 1, intercellular adhesion molecule Type 1, and E-selectin. The albumin index for the moyamoya group was 9, which was significantly higher than that for the control group. However, there were no differences in the serum levels of the three soluble adhesion molecules and no correlations between age, Suzuki classification, and serum and CSF levels of adhesion molecules. Our study demonstrates increased CSF levels of soluble endothelial adhesion molecules, suggesting that children with moyamoya syndrome have ongoing central nervous system inflammation, with slight impairment of the blood-brain barrier. These soluble adhesion molecules may be clinically useful as indicators of this inflammatory process and may provide some insight into this enigmatic disease process.