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

2018 ◽  
Vol 99 (4) ◽  
pp. 645-650
Author(s):  
O V Moskalets
Keyword(s):  
Cell Adhesion ◽  
Cell Membrane ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecules ◽  
Proteolytic Enzymes ◽  
Intercellular Adhesion Molecule ◽  
Critical States ◽  
Molecule Type

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.

Abstract 13301: Methylome-wide Association With Soluble Cell Adhesion Molecules Among Monozygotic Twins

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yan Sun ◽  
Jack Goldberg ◽  
Dean P Jones ◽  
Viola Vaccarino
Keyword(s):  
Cell Adhesion ◽  
Endothelial Function ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecules ◽  
Critical Role ◽  
Epigenetic Mechanism ◽  
Intercellular Adhesion Molecule ◽  
Soluble Form ◽  
Intercellular Adhesion Molecule 1

Introduction: Inflammation plays a critical role in the pathogenesis of cardiovascular disease. Epigenetic mechanisms, including DNA methylation (DNAm), is critical in the regulation of inflammatory genes, and can be influenced by inflammation. The soluble form of cell adhesion molecules, including vascular adhesion molecule 1 (sVCAM1), intercellular adhesion molecule 1 (sICAM1), and P-selectin (sP-selectin), are established biomarkers for inflammation and endothelial function, and are linked to cardiovascular events. Methods: To identify epigenetic markers associated with inflammation and endothelial function, we conducted a methylome-wide association study and investigated over 480,000 DNAm sites of peripheral blood cells from 140 monozygotic (MZ) middle-aged male twins from the Emory Twin Study. Results: Using two randomly selected subsets consisting of unrelated subjects, we identified and replicated 69 and 23 DNAm sites significantly associated with sVCAM1, and sICAM1 respectively, adjusted for multiple testing, but none for sP-selectin. All 23 sICAM1-associated DNAm sites were also associated with sVCAM1, including sites on gene ANKRD11 (P=1.51х10-21, 2.62х10-20), KDM2B (P=1.52х10-21, 9.13х10-17), CAPS (P=2.81х10-20, 3.17х10-18), and CUX1 (P=7.63х10-20, 2.84х10-19). They jointly explained 54% and 40% of variance in sVCAM1 and sICAM1 respectively. Two DNAm sites, located on UNC5D and TMEM125, were also significant comparing MZ twins who were phenotypically discordant for both sICAM1 (P=1.79х10-7, 2.78х10-6) and sVCAM1 (P=1.70х10-9, 1.71х10-7). Conclusions: These results suggest that sVCAM1 and sICAM1, but not sP-selectin, may share common pathophysiology in inflammation and endothelial function via an epigenetic mechanism in leukocytes. In addition, the epigenetic association with inflammation may be driven by unshared environmental exposures.

scholarly journals Circulating cell adhesion molecules in metabolically healthy obesity

2020 ◽  
Author(s):  
Arij Mulhem ◽  
Yusef Moulla ◽  
Nora Klöting ◽  
Thomas Ebert ◽  
Anke Tönjes ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecules ◽  
Intercellular Adhesion Molecule ◽  
Serum Concentrations ◽  
Metabolically Healthy Obesity ◽  
Intercellular Adhesion Molecule 1 ◽  
Increased Risk ◽  
Metabolically Healthy

Abstract Background/Objectives People with metabolically healthy obesity (MHO) may still have an increased risk for cardiovascular mortality compared to metabolically healthy lean (MHL) individuals. However, the mechanisms linking obesity to cardiovascular diseases are not entirely understood. We therefore tested the hypothesis that circulating cell adhesion molecules (CAMs) are higher in MHO compared to MHL individuals. Subjects/Methods Serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), E-selectin and P-selectin were measured in age- and sex-matched groups of MHL (n = 32), MHO categorized into BMI-matched insulin sensitive (IS, n = 32) or insulin resistant (IR) obesity (n = 32) and people with metabolically unhealthy obesity (MUO, n = 32). Results Indeed, individuals with MHO have significantly higher sICAM-1, E-selectin, and P-selectin serum concentrations compared to MHL people. However, these CAMs are still significantly lower in IS compared to IR MHO. There was no difference between the groups in sVCAM-1 serum concentrations. Compared to all other groups, circulating adhesion molecules were significantly higher in individuals with MUO. Conclusions These findings suggest that obesity-related increased cardiovascular risk is reflected and may be mediated by significantly higher CAMs. The mechanisms causing elevated adhesion molecules even in the absence of overt cardio-metabolic risk factors and whether circulating CAMs could predict cardiovascular events need to be explored.

scholarly journals Migration inhibitory factor up-regulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 via Src, PI3 kinase, and NFκB

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2252-2261 ◽  
Author(s):  
M. Asif Amin ◽  
Christian S. Haas ◽  
Kui Zhu ◽  
Pamela J. Mansfield ◽  
Michael J. Kim ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecules ◽  
Cell Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Dependent Manner ◽  
Vascular Cell Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Cell Adhesion Molecule 1

AbstractCell adhesion molecules are critical in monocyte (MN) recruitment in immune-mediated and hematologic diseases. We investigated the novel role of recombinant human migration inhibitory factor (rhMIF) in up-regulating vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and their signaling pathways in human MNs. rhMIF-induced expression of VCAM-1 and ICAM-1 was significantly higher compared with nonstimulated MNs. rhMIF induced MN VCAM-1 and ICAM-1 expression in a concentration-dependent manner (P < .05). Antisense oligodeoxynucleotides (ODNs) and inhibitors of Src, PI3K, p38, and NFκB significantly reduced rhMIF-induced MN VCAM-1 and ICAM-1 expression (P < .05). However, Erk1/2 and Jak2 were not involved. Silencing RNA directed against MIF, and inhibitors of Src, PI3K, NFκB, anti–VCAM-1, and anti–ICAM-1 significantly inhibited rhMIF-induced adhesion of HL-60 cells to human dermal microvascular endothelial cells (HMVECs) or an endothelial cell line, HMEC-1, in cell adhesion assays, suggesting the functional significance of MIF-induced adhesion molecules (P < .05). rhMIF also activated MN phospho-Src, -Akt, and -NFκB in a time-dependent manner. rhMIF induced VCAM-1 and ICAM-1 up-regulation in 12 hours via Src, PI3K, and NFκB as shown by Western blotting and immunofluorescence. MIF and MIF-dependent signaling pathways may be a potential target for treating diseases characterized by up-regulation of cell adhesion molecules.

Adhesion molecules, mycophenolate mofetil and systemic lupus erythematosus

Lupus ◽  
2005 ◽  
Vol 14 (3_suppl) ◽  
pp. 17-26 ◽  
Author(s):  
MJ Lewis ◽  
D D'Cruz
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mycophenolate Mofetil ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Lupus Erythematosus ◽  
Cell Adhesion Molecules ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Systemic Lupus

Mycophenolate mofetil (MMF) has been reproducibly shown to inhibit lymphocyte adhesion and penetration of endothelial cell surfaces. The mechanism is not yet elucidated. In vitro studies on the effects of MMF on cell adhesion molecules (CAM) using human umbilical vein endothelial cells (HUVEC) have shown conflicting results. Different studies have independently shown that MMF increased, decreased or had no effect on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1). Several studies suggest MMF may reduce the endothelial expression of E-selectin. Recent studies have been unable to replicate initial work, which suggested that MMF impaired glycosylation of lymphocyte CAM. The same studies concluded that MMF had no effect on the surface expression of lymphocyte CAM, but altered the binding ability of these molecules. ICAM-1/LFA-1 (lymphocyte function-associated antigen-1), VCAM-1/VLA-4 (very late antigen-4) and P-selectin/PSGL-1 (P-selectin glycoprotein ligand-1) ligand pairs are most likely to be involved. Few in vivo and no conclusive human studies have been carried out. The literature relevant to cell adhesion molecules in systemic lupus erythematosus (SLE) is reviewed in detail.

scholarly journals Elevated Expression of Serum Endothelial Cell Adhesion Molecules in COVID-19 Patients

2020 ◽  
Vol 222 (6) ◽  
pp. 894-898 ◽  
Author(s):  
Ming Tong ◽  
Yu Jiang ◽  
Da Xia ◽  
Ying Xiong ◽  
Qing Zheng ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecules ◽  
Serum Levels ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Endothelial Cell Adhesion Molecules ◽  
Endothelial Cell Adhesion

Abstract In a retrospective study of 39 COVID-19 patients and 32 control participants in China, we collected clinical data and examined the expression of endothelial cell adhesion molecules by enzyme-linked immunosorbent assays. Serum levels of fractalkine, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular adhesion protein-1 (VAP-1) were elevated in patients with mild disease, dramatically elevated in severe cases, and decreased in the convalescence phase. We conclude the increased expression of endothelial cell adhesion molecules is related to COVID-19 disease severity and may contribute to coagulation dysfunction.

Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival

2019 ◽  
Vol 50 (2) ◽  
pp. 115-125 ◽  
Author(s):  
Sonja Suvakov ◽  
Djurdja Jerotic ◽  
Tatjana Damjanovic ◽  
Natasa Milic ◽  
Tatjana Pekmezovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecules ◽  
Cox Regression ◽  
Esrd Patient ◽  
Predictive Ability ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1

Introduction: Overall survival of patients with end-stage renal disease (ESRD) remains poor. Oxidative stress is one of the major risk factors associated with mortality in this patient group. As glutathione S-transferases (GST) are well-established antioxidants, we hypothesized that a model including GST gene polymorphisms, oxidative damage byproducts and cell adhesion markers has a prognostic role in ESRD patient survival. Methods: A prospective study of 199 patients with ESRD on haemodialysis was conducted. GST genotype, oxidative stress byproducts and cell adhesion molecules were measured in plasma. Multivariate Cox regression and Kaplan-Meier survival analyses were performed to test the predictive ability of these parameters in the 8-year follow-up period. Results: GSTM1-null genotype was associated with significantly shorter overall (HR 1.6, p = 0.018) and cardiovascular-specific (HR 2.1, p = 0.010) survival. Oxidative stress byproducts (advanced oxidation protein products [AOPP], prooxidant-antioxidant balance [PAB], malondialdehyde [MDA]) and cell adhesion molecules (soluble vascular cell adhesion molecule-1 [sVCAM-1] and soluble intercellular adhesion molecule-1 [sICAM-1]) demonstrated a significant predictive role in terms of overall and cardiovascular survival. When 6 biomarkers (GSTM1 genotype, high AOPP/PAB/MDA/­sVCAM-1/sICAM-1) were combined into a scoring model, a significantly shorter overall and cardiovascular survival was observed for patients with the highest score (p < 0.001). Conclusion: We identified a novel panel of biomarkers that can be utilized in predicting survival in ESRD patients. This biomarker signature could enable better monitoring of patients and stratification into appropriate treatment groups.

scholarly journals Monocytic microparticles activate endothelial cells in an IL-1β–dependent manner

Blood ◽  
2011 ◽  
Vol 118 (8) ◽  
pp. 2366-2374 ◽  
Author(s):  
Jian-Guo Wang ◽  
Julie C. Williams ◽  
Beckley K. Davis ◽  
Ken Jacobson ◽  
Claire M. Doerschuk ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecules ◽  
Bacterial Infections ◽  
Mononuclear Cells ◽  
Intercellular Adhesion Molecule ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear

Abstract Microparticles (MPs) are shed from activated and dying cells. They can transmit signals from cell to cell, locally or at a distance through the circulation. Monocytic MPs are elevated in different diseases, including bacterial infections. Here, we investigated how monocytic MPs activate endothelial cells. We found that MPs from lipopolysaccharide (LPS)–treated THP-1 monocytic cells bind to and are internalized by human endothelial cells. MPs from LPS-treated THP-1 cells, but not untreated cells, induced phosphorylation of ERK1/2, activation of the nuclear factor-κB pathway and expression of cell adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. Similar results were observed using MPs from LPS-treated peripheral blood mononuclear cells. We next investigated the mechanism by which monocytic MPs activated endothelial cells and found that they contain IL-1β and components of the inflammasome, including apoptosis-associated speck-like protein containing a CARD, caspase-1, and NLRP3. Importantly, knockdown of NLRP3 in THP-1 cells reduced the activity of the MPs and blockade of the IL-1 receptor on endothelial cells decreased MP-dependent induction of cell adhesion molecules. Therefore, monocytic MPs contain IL-1β and may amplify inflammation by enhancing the activation of the endothelium.

scholarly journals Distinct Roles For ROCK1 and ROCK2 in the Regulation of Oxldl-Mediated Endothelial Dysfunction

2018 ◽  
Vol 49 (2) ◽  
pp. 565-577 ◽  
Author(s):  
Lei Huang ◽  
Fan Dai ◽  
Lian Tang ◽  
Xiaofeng Bao ◽  
Zhaoguo Liu ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Endothelial Dysfunction ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Apoptosis ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Rock Inhibitor ◽  
Vimentin Expression

Background/Aims: This study used Rho-associated protein kinase (ROCK) isoform-selective suppression or a ROCK inhibitor to analyze the roles of ROCK1 and ROCK2 in regulating endothelial dysfunction triggered by oxidized low-density lipoprotein (oxLDL). Methods: ROCK1 or ROCK2 expression in human umbilical vein endothelial cells (HUVECs) was suppressed by small interfering RNA (siRNA). HUVECs were pretreated with 30 μM Y27632 (pan ROCK inhibitor) for 30 min before exposure to 200 μg/mL oxLDL for an additional 24 h. Cell viability was determined by the MTT assay, and cell apoptosis was evaluated by the TUNEL assay. Protein expression and phosphorylation were assessed by Western blot analysis. The morphology of total and phosphorylated vimentin (p-vimentin) and the co-localization of vimentin with vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) were detected by the immunofluorescence assay. The adhesion of promonocytic U937 cells to HUVECs was observed by light microscopy. Results: ROCK2 suppression or Y27632 treatment, rather than ROCK1 deletion, effectively reduced endothelial cell apoptosis and preserved cell survival. ROCK2 suppression exhibited improved vimentin and p-vimentin cytoskeleton stability and decreased vimentin cleavage by attenuating caspase-3 activity. In addition, increased p-vimentin expression induced by oxLDL was significantly inhibited by ROCK2 deletion or Y27632 treatment. In contrast, ROCK1 suppression showed no obvious effects on the vimentin cytoskeleton, but significantly regulated the expression of adhesion molecules. Endothelial ICAM-1 or VCAM-1 expression induced by oxLDL was obviously inhibited by ROCK1 suppression or Y27632 treatment. Moreover, the expression of ICAM-1 induced by oxLDL could also be reduced by ROCK2 suppression. Furthermore, ROCK2 deficiency or Y27632 treatment inhibited the redistribution of adhesion molecules and their co-localization with vimentin caused by oxLDL. These effects resulted in the significant inhibition of monocyte-endothelial adhesion induced by oxLDL. Conclusion: The results of this study support the novel concept that ROCK1 is involved in oxLDL-induced cell adhesion by regulating adhesion molecule expression, whereas ROCK2 is required for both endothelial apoptosis and adhesion by regulating both the vimentin cytoskeleton and adhesion molecules. Consequently, ROCK1 and ROCK2 have distinct roles in the regulation of oxLDL-mediated endothelial dysfunction.

Sign in / Sign up

Export Citation Format

Share Document