Effects of pulse methylprednisolone on cell adhesion molecules in the synovial membrane in rheumatoid arthritis. Reduced E-selectin and intercellular adhesion molecule 1 expression

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.

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Circulating cell adhesion molecules in metabolically healthy obesity

International Journal of Obesity ◽

10.1038/s41366-020-00667-4 ◽

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.

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

Blood ◽

10.1182/blood-2005-05-2011 ◽

2006 ◽

Vol 107 (6) ◽

pp. 2252-2261 ◽

Cited By ~ 95

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.

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A Circadian Variation Exists for Soluble Levels of Intercellular Adhesion Molecule-I and E-Selectin in Healthy Volunteers

Clinical Science ◽

10.1042/cs0940537 ◽

1998 ◽

Vol 94 (5) ◽

pp. 537-540 ◽

Cited By ~ 22

Author(s):

C. Maple ◽

G. Kirk ◽

M. McLaren ◽

D. Veale ◽

J.J.F. Belch

Keyword(s):

Cell Adhesion ◽

Disease Activity ◽

Diurnal Variation ◽

Adhesion Molecule ◽

Cell Adhesion Molecules ◽

Circadian Variation ◽

Intercellular Adhesion ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Soluble Intercellular Adhesion Molecule

1. We have previously shown a circadian variation in leucocyte activation and endothelial function which may explain why some inflammatory and vascular diseases show a circadian variation in disease activity/occurrence. 2. We have investigated the circadian variation of two soluble cell adhesion molecules, intercellular adhesion molecule-1 and E-selectin, in 10 healthy volunteers. Soluble intercellular adhesion molecule-1 is released from both activated leucocytes and endothelial cells while soluble E-selectin is released only from activated endothelium. 3. Results show a circadian variation exists for both soluble intercellular adhesion molecule-1 and E-selectin (both P < 0.0001, analysis of variance) with a peak activity at 12:00 h for both measures and a minimum activity at 04:00 h for intercellular adhesion molecule-1 and 00:00 h for E-selectin. 4. These results demonstrate the existence of a diurnal variation in cell adhesion molecules, providing evidence in support of a diurnal pattern in endothelial and leucocyte activation. An alteration in this biological rhythm may help to explain the diurnal variation in disease activity in certain inflammatory and vascular disease states. Furthermore, it stresses the importance of sample time point standardization in clinical studies.

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

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa349 ◽

2020 ◽

Vol 222 (6) ◽

pp. 894-898 ◽

Cited By ~ 8

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.

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Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival

American Journal of Nephrology ◽

10.1159/000501300 ◽

2019 ◽

Vol 50 (2) ◽

pp. 115-125 ◽

Cited By ~ 5

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.

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