Endothelial Leukocyte Adhesion Molecule-1 Research Articles

Vascular Cell Adhesion Molecule-1 and Endothelial Leukocyte Adhesion Molecule-1 as Markers of Atherosclerosis of NIDDM

Background: Leukocyte adhesion to arterial endothelial cells is thought to be an important step in the development of atherosclerosis, Adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and the endothelial-leukocyte adhesion molecule-1 (ELAM-1) play an essential role in the early stages of atherogenesis of diabetic patients. Materials and Methods: The study was conducted on 80 male divided into two groups 60 of them had diabetes mellitus and 20 subjects were normal healthy individuals served as a control group. Enzyme linked immune sorbent assay (ELISA) was used for the measurement of serum VCAM-1and ELAM-1and WBC assay executed by automatic hematology analyzer the information of patients were obtained through a questionnaire consisted Patients with other diseases were excluded from the current investigation. Results: This result revealed elevated level of serum VCAM-1and ELAM-1 of Diabetes patients compared with healthy group also differentiation count reveal elevated count of WBC, Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil in Diabetes patient as compare with HT group.

Co-culture of endothelial cells and patterned smooth muscle cells on titanium: Construction with high density of endothelial cells and low density of smooth muscle cells

Endothelialization has been considered a promising method to improve the biocompatibility of vascular implanted biomaterials. However, little is known about the anti-coagulation, anti-inflammatory, anti-atherosclerosis and anti-shedding property of the attached endothelial cells (ECs) and the relationship with their bio-environment and material-environment, which are both important evaluations to the cardiovascular biomaterials designed for tissue engineering applications and in vivo implantation. In this in vitro study, a novel co-culture model was built, where vascular smooth muscle cells (SMCs) were cultured on the hyaluronic acid (HA) micro-strip patterned titanium (Ti) surface on a low density to biomimetic the EC pericyte environment. Subsequently, the EC number and its functional factor, including nitric oxide (NO), prostacyclin (PGI2), tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), and the inflammatory induced factor, endothelial leukocyte adhesion molecule-1 (E-selectin) were quantified, respectively. The anti-shedding property was also assessed by the blood flow shear stress (BFSS) acting. The results showed that the novel co-culture model possessed better EC coverage, functional factor release and anti-shedding functions than the control.

Ultrasound Detection of Myocardial Ischemic Memory Using an E-Selectin Targeting Peptide Amenable to Human Application

Vascular endothelial leukocyte adhesion molecules, such as E-selectin, are acutely upregulated in myocardial ischemia/reperfusion and are thus "ischemic memory" biomarkers for recent cardiac ischemia. We sought to develop an ultrasound molecular imaging agent composed of microbubbles (MBs) targeted to E-selectin to enable the differential diagnosis of myocardial ischemia in patients presenting with chest pain of unclear etiology. Biodegradable polymer MBs were prepared bearing a peptide with specific human E-selectin affinity (MBESEL). Control MBs had scrambled peptide (MBCTL) or nonspecific IgG (MBIgG). MBESEL adhesion to activated rat endothelial cells (ECs) was confirmed in vitro in a flow system and in vivo with intravital microscopy of rat cremaster microcirculation. Ultrasound molecular imaging of recent myocardial ischemia was performed in rats 4 hours after transient (15 minutes) coronary occlusion. MBESEL adhesion was higher to inflamed versus normal ECs in vitro; there was no difference in MBCTL or MBIgG adhesion to inflamed versus normal ECs. There was greater adhesion of MBESEL to inflamed versus noninflamed microcirculation and minimal adhesion of MBCTL or MBIgG under any condition. Ultrasound imaging after injection of MBSEL demonstrated persistent contrast enhancement of the previously ischemic region. Videointensity in postischemic myocardium after MBESEL was higher than that in the nonischemic bed (11.6 ± 2.7 dB vs 3.6 ± 0.8 dB, p < .02) and higher than that after MBCTL (4.0 ± 1.0 dB, p < .03) or MBIgG (1.7 ± 0.1 dB, p < .03). MBs targeted to E-selectin via a short synthetic peptide with human E-selectin binding affinity enables echocardiographic detection of recent ischemia, setting the stage for clinical myocardial ischemic memory imaging to identify acute coronary syndromes.

Infusion of 7.2% NaCl/6% Hydroxyethyl Starch 200/0.5 in On-Pump Coronary Artery Bypass Surgery Patients

NaCl 7.2%/6% hydroxyethyl starch (HES) 200/0.5 (HSH) has shown its beneficial effects in cardiac surgery and immunomodulatory values in experiment and human studies. However, there is concern regarding detrimental renal effects of chloride and HES in the intensive care setting. The objective of this study was to evaluate the influence of HSH on kidney integrity and the level of inflammatory mediators in on-pump coronary artery bypass surgery patients. This was a single-center, prospective, randomized, single-blind pilot study. This work was performed at a tertiary cardiothoracic referral center during the period from February to August 2012. Forty patients scheduled for on-pump coronary artery bypass surgery were included. PATIENTS were randomized to receive once either 7.2% NaCl/6% HES 200/0.5 (HSH group, n = 20) or placebo (0.9% NaCl; control group, n = 20) at a dose of 4 mL·kg for 30 min after anesthesia induction. The primary end point was the incidence of acute kidney injury (AKI) defined according to the Kidney Disease: Improving Global Outcomes. Secondary end points were peak serum cystatin C, peak urine neutrophil gelatinase-associated lipocalin, plasma levels of interleukin 6 (IL-6), IL-10, intercellular adhesion molecule 1, and endothelial-leukocyte adhesion molecule (E-selectin). The incidence of AKI within 48 h was similar between the groups (HSH: four patients [20%]; control: six patients [30%]). There was a significantly lower peak value for serum cystatin C in the HSH group (0.83 [0.73-0.89] mg·L) compared with the control group (1.02 [0.88-1.15] mg·L; P = 0.001). PATIENTS in both groups had similar peak postoperative urine neutrophil gelatinase-associated lipocalin concentrations. NaCl 7.2%/6% hydroxyethyl starch 200/0.5 significantly reduces levels of IL-6 and IL-10 at 4 h after cardiopulmonary bypass and intercellular adhesion molecule 1 and E-selectin at 4 h after cardiopulmonary bypass and on postoperative day 1 (P < 0.05 for all). NaCl 7.2%/6% hydroxyethyl starch 200/0.5 does not lead to the increase in AKI incidence when used for the volume therapy in on-pump coronary artery bypass surgery patients. NaCl 7.2%/6% hydroxyethyl starch 200/0.5 usage enhanced neither tubular injury nor alteration of glomerular filtration. In addition, HSH can reduce the level of the inflammatory mediators after surgery.

Endothelial activation and repair during hantavirus infection: association with disease outcome.

Background. Endothelial activation and dysfunction play a central role in the pathogenesis of sepsis and viral hemorrhagic fevers. Hantaviral disease is a viral hemorrhagic fever and is characterized by capillary dysfunction, although the underlying mechanisms for hantaviral disease are not fully elucidated.Methods. The temporal course of endothelial activation and repair were analyzed during Puumala hantavirus infection and associated with disease outcome and a marker for hypoxia, insulin-like growth factor binding protein 1 (IGFBP-1). The following endothelial activation markers were studied: endothelial glycocalyx degradation (syndecan-1) and leukocyte adhesion molecules (soluble vascular cellular adhesion molecule 1, intercellular adhesion molecule 1, and endothelial selectin). Cytokines associated with vascular repair were also analyzed (vascular endothelial growth factor, erythropoietin, angiopoietin, and stromal cell-derived factor 1).Results. Most of the markers we studied were highest during the earliest phase of hantaviral disease and associated with clinical and laboratory surrogate markers for disease outcome. In particular, the marker for glycocalyx degradation, syndecan-1, was significantly associated with levels of thrombocytes, albumin, IGFBP-1, decreased blood pressure, and disease severity.Conclusions. Hantaviral disease outcome was associated with endothelial dysfunction. Consequently, the endothelium warrants further investigation when designing future medical interventions.

Amla (Emblica officinalisGaertn.) extract inhibits lipopolysaccharide-induced procoagulant and pro-inflammatory factors in cultured vascular endothelial cells

Amla (Emblica officinalis Gaertn.) has been used for many centuries in traditional Indian Ayurvedic formulations for the prevention and treatment of many inflammatory diseases. The present study evaluated the anti-inflammatory and anticoagulant properties of amla fruit extract. The amla fruit extract potentially and significantly reduced lipopolysaccharide (LPS)-induced tissue factor expression and von Willebrand factor release in human umbilical vein endothelial cells (HUVEC) in vitro at clinically relevant concentrations (1-100 μg/ml). In a leucocyte adhesion model of inflammation, it also significantly decreased LPS-induced adhesion of human monocytic cells (THP-1) to the HUVEC, as well as reduced the expression of endothelial-leucocyte adhesion molecule-1 (E-selectin) in the target cells. In addition, the in vivo anti-inflammatory effects were evaluated in a LPS-induced endotoxaemia rat model. Oral administration of the amla fruit extract (50 mg/kg body weight) significantly decreased the concentrations of pro-inflammatory cytokines, TNF-α and IL-6 in serum. These results suggest that amla fruit extract may be an effective anticoagulant and anti-inflammatory agent.

IgG anti–NR2 glutamate receptor autoantibodies from patients with systemic lupus erythematosus activate endothelial cells

To investigate the possibility that IgG anti-NR2 glutamate receptor antibodies (anti-NR2) derived from patients with systemic lupus erythematosus (SLE) cause an immunologic interaction with endothelial cells (ECs) in the blood-brain barrier, resulting in inflammation of the blood-brain barrier, allowing the entrance of these autoantibodies into the cerebrospinal fluid. Purified IgG anti-NR2 antibodies from 14 patients with SLE were tested for their ability to bind to double-stranded DNA (dsDNA) and ECs, to modulate endothelial adhesion molecule expression and cytokine production by ECs, and to activate the NF-κB pathways in the ECs. Purified IgG from 5 normal subjects was used as a negative control. Purified IgG anti-NR2 antibodies bound to dsDNA in an IgG-dose-dependent manner. This interaction up-regulated the expression of endothelial leukocyte adhesion molecule 1, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 on the EC surface and increased the production of interleukin-6 (IL-6) and IL-8, but not tumor necrosis factor α or IL-1β, by ECs. Purified IgG anti-NR2 also activated the degradation of cytoplasmic IκB, indicating the activation of NF-κB in the ECs. EC activation through the NF-κB signaling pathway induced by IgG anti-NR2 antibodies in the central nervous system of SLE patients may lead to inflammation of the blood-brain barrier, initiating the pathogenesis of neuropsychiatric SLE.

Estimating the risk after gestational diabetes mellitus: can we improve the information from the postpartum OGTT?

Risk stratification after pregnancy with gestational diabetes mellitus (GDM) is based on screening with the 2-h oral glucose tolerance test (OGTT). Actually, prediabetes and diabetes are diagnosed by impaired fasting [fasting plasma glucose (FPG)] and 120 min-postload glucose levels (120'-PLG). We hypothesized that the clinical information could be improved by including measurements at different time points from the OGTT in the medical decision-making process. One hundred ten women with previous gestational diabetes (pGDM) and 41 controls were included 3-6 mo after delivery and underwent specific metabolic assessments: 3-h OGTT, frequently sampled intravenous glucose tolerance test (FSIGT) with markers of inflammation and endothelial function. pGDMs were annually invited for reexaminations for a maximum of 10 yr. Multiple linear regression suggested that postload glucose levels at 60 min (60'-PLG) were a better predictor for insulin sensitivity [β: -0.10, 95% confidence interval (CI) -0.14 to -0.05, P < 0.001] and disposition index (DI) (β: -0.07, 95% CI -0.12 to -0.02, P = 0.004) estimated from the FSIGT compared with other time points during the OGTT. The association between 60'-PLG and insulin secretion was of particular importance in women after GDM. We further identified associations of 60'-PLG with ultrasensitive C-reactive protein, plasminogen activator inhibitor 1, tissue plasminogen activator, endothelial-leukocyte adhesion molecule 1, and intercellular adhesion molecule (ICAM)-1. There appeared to be no interactions between females with pGDM and controls, suggesting comparable effects. We observed that 60'-PLG levels were closely related to the later onset of diabetes independent from the routinely measured FPG and 120'-PLG levels. Our data suggest that the sole interpretation of FPG and 120'-PLG of the OGTT leads to significant loss of information. Particularly 60'-PLG was shown to distinguish women at low or high metabolic and cardiovascular risk.

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...

SIMVASTATIN PREVENT ATHEROSCLEROSIS DEVELOPMENT THROUGH INHIBITING PROTEIN EXPRESSION OF ADHESION MOLECULES

ObjectivesTo explore the effects of simavastatin on protein expressions of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial leukocyte adhesion molecule 1 (E-selectin) of cholesterol...

4F, apolipoprotein AI mimetic peptide, attenuates acute lung injury and improves survival in endotoxemic rats

4F, apolipoprotein AI mimetic peptide, mimics anti-inflammatory properties of high-density lipoprotein (HDL). The aim of this study was to investigate whether 4F attenuates acute lung injury and improves survival in endotoxemic rats and to determine whether the therapeutic benefits of 4F are associated with the stimulation of sphingosine-1-phosphate receptor 1 (S1P1), the activation of Akt, the down-regulation of the nuclear factor-κB (NF-κB) pathway, and the suppression of cell adhesion molecules. To induce endotoxemia in rats, lipopolysaccharide (LPS, 10 mg/kg) was injected into a tail vein and 10 minutes later, vehicle or 4F (10 mg/kg) was administered intraperitoneally, respectively. We observed the survival of subjects for 72 hours. At 6-hour post-LPS, we killed animals and measured S1P1 expression, phosphorylated Akt/Akt ratio, cytoplasmic phosphorylated inhibitor κB-α/inhibitor κB-α ratio, nuclear NF-κB p65 expression and DNA-binding activity, endothelial leukocyte adhesion molecule-1 (E-selectin) and intercellular adhesion molecule-1 expression, myeloperoxidase activity, and histologic damages in lung tissues. We also measured serum HDL cholesterol level. 4F improved survival in endotoxemic rats. 4F restored LPS-induced diminution of serum HDL cholesterol level and increased lung S1P1 expression and phosphorylated Akt/Akt ratio in LPS-treated rats. Furthermore, 4F suppressed inhibitor κB-α degradation, NF-κB activation, E-selectin and intercellular adhesion molecule-1 expression, and myeloperoxidase activity, and attenuated histologic damages in lung tissues. 4F attenuated acute lung injury and improved survival in endotoxemic rats. The therapeutic benefits of 4F were found to be associated with the stimulation of S1P1, the activation of Akt, the down-regulation of the NF-κB pathway, and the suppression of cell adhesion molecules.

Long-term ethanol consumption initiates atherosclerosis in rat aorta through inflammatory stress and endothelial dysfunction

Controversy exists on whether alcohol has a direct cardioprotective effect or it provokes atherosclerosis, so the present study sought to assess the effect of chronic consumption of ethanol on the markers of endothelial function, vessel rigidity, and atherosclerosis in the aorta of rat. Male Wistar rats were selected randomly and exposed to ethanol (4.5g⁄kg of 20% w/v solution in saline) once per day for 6weeks. Blood pressure, hemodynamic parameters, foam cell formation, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial-leukocyte adhesion molecule-1, and high-sensitivity C-reactive protein (CRP) were assessed in ethanol treated rats and compared with either sham or control rats. The results revealed a concurrent significant increase of adhesion molecules, CRP levels, systolic, diastolic, pulse, and dicrotic pressures as well as enhanced formation of foam cell in ethanol-treated rats. These findings implicate that long-term ethanol exposure provokes atherogenic and hemodynamic changes via significant induction of proinflammatory response, augmenting of cell adhesion molecules, stiffness in rat aorta wall and induction of foam cell formation.

Engineered endothelial cell adhesion via VCAM1 and E-selectin antibody-presenting alginate hydrogels

Materials that adhere to the endothelial cell (EC) lining of blood vessels may be useful for treating vascular injury. Cell adhesion molecules (CAMs), such as endothelial leukocyte adhesion molecule-1 (E-selectin) and vascular cell adhesion molecule-1 (VCAM1), modulate EC–leukocyte interactions. In this study, we mimicked cell–cell interactions by seeding cells on alginate hydrogels modified with antibodies against E-selectin and VCAM1, which are upregulated during inflammation. ECs were activated with interleukin-1α to increase CAM expression and subsequently seeded onto hydrogels. The strength of cell adhesion onto gels was assessed via a centrifugation assay. Strong, cooperative EC adhesion was observed on hydrogels presenting a 1:1 ratio of anti-VCAM1:anti-E-selectin. Cell adhesion was stronger on dual functionalized gels than on gels modified with anti-VCAM1, anti-E-selectin or the arginine–glycine–aspartic acid (RGD) peptide alone. Anti-VCAM1:anti-E-selectin-modified hydrogels may be engineered to adhere the endothelium cooperatively.

Inhibitory CpG sequences reduced ischemia/reperfusion-induced hepatic metastases of liver tumor in a murine model

BackgroundIt is reported that hepatic ischemia/reperfusion (I/R) during hepatectomy accelerates liver tumor growth. Hepatic I/R induces inflammation cytokines, which can accelerate the outgrowth of liver tumor. Inhibitory CpG sequence (iCpG) is an inhibitor of TLR9, which plays an important role in hepatic I/R. The aim of this study was to examine whether iCpG could prevent hepatic I/R-induced metastases of the liver tumor. Materials and methodsA murine tumor model that underwent partial hepatic I/R or sham operation was treated with iCpG or control DNA sequence (Ctrl ODN). Tumor growth and metastases were observed on day 14 after surgery; Endothelial leukocyte adhesion molecules such as E-selectin and intracellular adhesion molecule-1 (ICAM-1) protein expression were measured 24 h after reperfusion by Western blotting; E-selectin and ICAM-1 mRNA expression in hepatic tissue was measured 2 h after reperfusion by RT-PCR; NF-κB activity in hepatic tissue was measured 2 h after reperfusion by electrophoretic gel mobility shift assay. ResultsThe tumor growth in the mice subjected to hepatic I/R was remarkably stimulated when compared with the mice subjected to laparotomy alone. The iCpG had no significant inhibitory effect on tumor growth in sham-operated mice subjected to tumor. However, iCpG could reduce the tumor growth and inhibit the activation of NF-κB and downregulate the E-selectin and ICAM-1 mRNA and protein in the mice with tumor subjected to I/R. ConclusionsICpG might reduce I/R-induced hepatic metastases of liver tumor cells by inhibiting NF-κB expression and downregulating the adhesive molecules, such as E-selectin and ICAM-1.

The Effect of Soy Protein Beverages on Serum Cell Adhesion Molecule Concentrations in Prehypertensive/Stage 1 Hypertensive Individuals

Objective: Prehypertensive and hypertensive individuals are at increased risk of atherosclerotic cardiovascular disease (CVD), in part because hypertension contributes to endothelial dysfunction and increased cell adhesion molecule expression. Soy protein and isoflavones may favorably alter CVD risk factors, and hence the aim of this study was to determine whether intake of cow's milk compared with soy beverage prepared from whole soy bean (WSB) or soy protein isolate (SPI) would lower soluble cell adhesion molecule concentrations as a means of decreasing CVD risk.Methods: We enrolled healthy prehypertensive/stage 1 hypertensive men (n = 60; 18–63 years) and premenopausal women (n = 8; 20–48 years). Participants were randomized to 1 of 3 groups for 8 weeks: cow's milk (600 mL/d), SPI beverage (840 mL/d; 30.1 mg total isoflavones/d), or WSB beverage (840 mL/d; 91.4 mg total isoflavones/d). We measured soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and endothelial-leukocyte adhesion molecule-1 (E-selectin) concentrations at baseline and week 8.Results: Soluble CAM concentrations were not altered by treatment and did not differ between prehypertensive and hypertensive participants. However, analysis of variance indicated a treatment × gender interaction (gender effect) for ICAM-1 (p = 0.0037) but not for E-selectin (p = 0.067) or VCAM-1 (p = 0.16). Men had higher concentrations of ICAM-1 and E-selectin, respectively, at baseline (p = 0.0071, p = 0.049) and week 8 (p = 0.0054, p = 0.038) than women did.Conclusion: Neither intake of cow's milk nor soy beverage for 8 weeks altered soluble CAM concentrations in prehypertensive/stage 1 hypertensive individuals, suggesting that neither type of beverage diminished atherosclerotic CVD risk in mildly hypertensive individuals by way of improving circulating CAM concentrations.

Optimization of Protein Immobilization in Microfludic Devices for Circulating Tumor Cell Capture

The isolation of metastatic circulating tumor cells (CTCs) within the blood using microfluidic devices is a promising method for the detection of cancer. In this study, protein patterning of endothelial-leukocyte adhesion molecule-1 (E-selectin) and anti-epitheal-cell-adhesion-molecule (Anti-EpCAM) within microfluidic channels is utilized to improve the capture efficiency. To create this protein patterning the protein immobilization method must first be optimized to allow for maximum capture of CTCs and minimal increase in the flow rate of cells through the device due to added coating thickness. Proteins are immobilized in alternating regions using photo-initiated graft polymerization of polyacrylic acid (PAA) and a silanization reaction. Using interferometer measurements and fluorescent tagging, PAA height was minimized and protein immobilization was optimized.

PP-099 IS THERE ANY RELATION BETWEEN CIRCULATING ENDOTHELIAL-LEUKOCYTE ADHESION MOLECULE-1 AND EXTENT OF CORONARY ARTERY INVOLVEMENTS IN MEN WITH ANGINA PECTORIS?

Background-Selectins as a group of adhesion molecule arise from the surface of activated cell and involved for atherosclerotic plaque production. Objective-To evaluate the relationship between Circulating Endothelial-Leukocyte adhesion molecule -1 (E-selectin) and the extent of coronary artery involvement in male Patients with coronary heart disease (CHD). MethodsParticipants were 103 male patients with symptoms of CHD. Patients underwent coronary angiography and according to angiography results they were divided to 80 patients with severe CHD and 23 with mild coronary involvements according to angiographic score. The Circulating E-selectin level was compared in both groups by ELISA method. Anova and analysis of covariant (ANCOVA) were used for evaluating possible association of E-selectin level and severity of coronary artery involvement by adjusting age, history of diabetes mellitus, hypertension, and dyslipidemia. ResultsThe mean age of 103 male patients was 58.32±9.42 years. The E-selectin level was not significantly different in both groups with sever and minimal (CHD) (P=0.78). ANCOVA test could not show after significant association between E-selectin level and the extent of coronary artery involvement adjusting age (P=0.94) as well as history of diabetes mellitus, hypertension, and dyslepidemia respectively (P=0.43). ConclusionThe circulating E-selectin level have no association with the severity of CHD in male patients(Iranian Heart Journal 2011; 12 (4):37-42). Key Word : Adhesion molecule■ E-selectin■ CAD■ coronary angiography■ extent Received June. 16, 2011; Accepted for publication Feb. 10, 2012 1. Associated Professor of Cardiology, Cardiac Rehabilitation Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran. 2. Assistant Researcher, Cardiac Rehabilitation Research Center, Isfahan Cardiovascular research Institute, Isfahan University of Medical Sciences, Isfahan, Iran. 3. Cardiology Fellow, Cardiovascular Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical sciences, Isfahan, Iran. 4. MS, MS, Biologist, Cardiovascular Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical sciences, Isfahan, Iran. 5. Researcher, Cardiac Rehabilitation Research Center, Isfahan Cardiovascular Research Institute, Isfahan, Iran. 6. Professor of Cardiology, Cardiovascular Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical sciences, Isfahan, Iran. Correspondence to: Masoumeh Sadeghi, MD. Head of CVD in Women Department Isfahan Cardiovascular Research Institute WHO Collaborating Center. (http://crc.mui.ac.ir) Isfahan University of Medical Sciences (http://mui.ac.ir) PO BOX: 81465-1148 Phone: +98 311 3359797 Fax: +98 311 3373435 Email: sadeghimasoumeh@gmail.com Ar ch iv of S ID

Dual functionalized PVA hydrogels that adhere endothelial cells synergistically

Cell adhesion molecules govern leukocyte-endothelial cell (EC) interactions that are essential in regulating leukocyte recruitment, adhesion, and transmigration in areas of inflammation. In this paper, we synthesized hydrogel matrices modified with antibodies against vascular cell adhesion molecule-1 (VCAM1) and endothelial leukocyte adhesion molecule-1 (E-Selectin) to mimic leukocyte-EC interactions. Adhesion of human umbilical vein ECs to polyvinyl alcohol (PVA) hydrogels was examined as a function of the relative antibody ratio (anti-VCAM1:anti-E-Selectin) and substrate elasticity. Variation of PVA backbone methacrylation was used to affect hydrogel matrix stiffness, ranging from 130 to 720 kPa. Greater EC adhesion was observed on hydrogels presenting 1:1 anti-VCAM1:anti-E-Selectin than on gels presenting either arginine-glycine-asparagine (RGD) peptide, anti-VCAM1, or anti-E-Selectin alone. Engineered cell adhesion - based on complementing the EC surface presentation - may be used to increase the strength of EC-matrix interactions. Hydrogels with tunable and synergistic adhesion may be useful in vascular remodeling.

Conformational Search on the Lewis X Structure by Molecular Dynamic: Study of Tri- and Pentasaccharide

Carbohydrates play vital roles in many biological processes, such as recognition, adhesion, and signalling between cells. The Lewis X determinant is a trisaccharide fragment implicated as a specific differentiation antigen, tumor antigen, and key component of the ligand for the endothelial leukocyte adhesion molecule, so it is necessary or essential to determine and to know their conformational and structural properties. In this work, conformational analysis was performed using molecular dynamics (MD) simulation with the AMBER10 program package in order to study the dynamic behavior of of the Lewis X trisaccharide (β-D-Gal-(1,4)-[α-L-Fuc-(1,3)]-β-D-GlcNAc-OMe) and the Lewis X pentasaccharide (β-D-Gal-(1,4)-[α-L-Fuc-(1,3)]-β-D-GlcNAc-(1,3)-β-D-Gal-(1,4)-β-D-Glu-OMe) in explicit water model at 300 K for 10 ns using the GLYCAM 06 force field.

Attenuation of Ischemia/Reperfusion Injury in Rats by the Anti-inflammatory Action of Resveratrol

Resveratrol (trans-3,4',5-trihydroxystilbene, CAS 501-36-0), a natural antioxidant and polyphenol found in grapes and wine, has been found to pharmacologically precondition the heart in nitric oxide (NO)-dependent manner. In the vascular system, NO functions as an endogenous inhibitor of leukocyte chemotaxis, adherence, and activation. The present study was designed to determine if resveratrol, through NO, can block the proadhesive molecules generated in the ischemic reperfused myocardium. Isolated hearts were prepared from properly anesthetized rats, and mounted on a Langendorff apparatus. The hearts were randomly assigned to one of the three groups: (i) control, (ii) resveratrol, and (iii) resveratrol + NG-nitro-L-arginine ethyl ester (L-NAME). The hearts were perfused in the absence (n = 6) or presence of 10 micromol/L resveratrol (n=6) or resveratrol + L-NAME (n = 6) for 15 min. All the hearts were then subjected to 30 min ischemia followed by 2 h of reperfusion. Ventricular function was monitored, infarct size and apoptotic cell death measured, and the proadhesive molecules and malonaldehyde formation determined in the perfusate. Resveratrol significantly improved postischemic ventricular function and reduced myocardial infarct size compared to the non-treated control group. The amount of proadhesive molecules including soluble intracellular adhesion molecule-1 (sICAM-1), endothelial leukocyte adhesion molecule-1 (sE-Selectin) and vascular cell adhesion molecule-1 (sVCAM-1) were each significantly decreased during reperfusion in the resveratrol group. L-NAME, a NO blocker, completely abolished such beneficial effects of resveratrol. The results support an anti-inflammatory action of resveratrol through a NO-dependent mechanism.