ErbB2 Expression on Left Ventricular Epicardial Endothelial Cells and CD105+ Cells is Decreased in Patients with Diabetes Mellitus.

2021 ◽  
Author(s):  
Joanne T. deKay ◽  
Joshua Carver ◽  
Bailey Shevenell ◽  
Angela M. Kosta ◽  
Sergey Tsibulnikov ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Cells ◽  
Cell Surface ◽  
High Glucose ◽  
Artery Bypass ◽  
Surface Expression ◽  
Left Ventricular ◽  
Cell Surface Expression ◽  
Erbb Receptors ◽  
Diabetic Patients

Abstract Background We investigated the cell surface expression of ErbB receptors on left ventricular (LV) epicardial endothelial cells and CD105+ cells obtained from cardiac biopsies of patients undergoing coronary artery bypass grafting surgery (CABG). Methods Endothelial cells and CD105+ non-endothelial cells were freshly isolated from LV epicardial biopsies obtained from 15 subjects with diabetes mellitus (DM) and 8 controls. The expression of ErbB recepotrs was examined using multiparametric flow cytometry. Human microvascular endothelial cells (HMEC-1) and LV epicardial CD105+ non-endothelial cells were used to determine the effect of high glucose on ADAM10-dependent cleavage of ErbB receptors. Results We found that diabetes mellitus (DM) and high levels of hemoglobin A1C are associated with reduced expression of ErbB2 on both endothelial cells and CD105+ non-endothelial cells. To determine if the expression of ErbB2 receptors is regulated by glucose levels, we examined the effect of high glucose in HMEC-1 and LV epicardial CD105+ non-endothelial cells, using a novel flow cytometric approach to simultaneously determine the total level, cell surface expression, and phosphorylation of ErbB2. Incubation of cells in the presence of 25 mM D-glucose resulted in decreased cell surface expression of ErbB2. We also found high expression of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) on both endothelial cells and CD105+ non-endothelial cells. Inhibition of ADAM10 prevented the high glucose-dependent decrease in the cell surface expression of ErbB2. Conclusions We suggest that high glucose depresses ErbB receptor signaling in endothelial cells and cardiac progenitor cells via the promotion of ADAM10-dependent cleavage of ErbB2 at the cell surface, thus contributing to vascular dysfunction and adverse remodeling seen in diabetic patients.

Perfusion with sickle erythrocytes up-regulates ICAM-1 andVCAM-1 gene expression in cultured human endothelial cells

Blood ◽  
2000 ◽  
Vol 95 (10) ◽  
pp. 3232-3241 ◽  
Author(s):  
Yan-Ting Shiu ◽  
Mark M. Udden ◽  
Larry V. McIntire
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Sickle Cell ◽  
Cell Adhesion Molecules ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Human Endothelial Cells ◽  
Sickle Erythrocytes

Sickle cell anemia is characterized by periodic vasoocclusive crises. Increased adhesion of sickle erythrocytes to vascular endothelium is a possible contributing factor to vasoocclusion. This study determined the effect of sickle erythrocyte perfusion at a venous shear stress level (1 dyne/cm2) on endothelial cell (EC) monolayers. Sickle erythrocytes up-regulated intercellular adhesion molecule-1 (ICAM-1) gene expression in cultured human endothelial cells. This was accompanied by increased cell surface expression of ICAM-1 and also elevated release of soluble ICAM-1 molecules. Expression of vascular cell adhesion molecule-1 (VCAM-1) messenger RNA (mRNA) was also strikingly elevated in cultured ECs after exposure to sickle cell perfusion, although increases in membrane-bound and soluble VCAM-1 levels were small. The presence of cytokine interleukin-1β in the perfusion system enhanced the production of ICAM-1 and VCAM-1 mRNA, cell surface expression, and the concentrations of circulating forms. This is the first demonstration that sickle erythrocytes have direct effects on gene regulation in cultured human ECs under well-defined flow environments. The results suggest that perfusion with sickle erythrocytes increases the expression of cell adhesion molecules on ECs and stimulates the release of soluble cell adhesion molecules, which may serve as indicators of injury and/or activation of endothelial cells. The interactions between sickle red blood flow, inflammatory cytokines, and vascular adhesion events may render sickle cell disease patients vulnerable to vasoocclusive crises.

scholarly journals Cell Surface Expression of LDL Receptor Is Decreased in Type 2 Diabetic Patients and Is Normalized by Insulin Therapy

Diabetes Care ◽  
2003 ◽  
Vol 26 (5) ◽  
pp. 1540-1544 ◽  
Author(s):  
L. Duvillard ◽  
E. Florentin ◽  
G. Lizard ◽  
J.-M. Petit ◽  
F. Galland ◽  
...  
Keyword(s):  
Cell Surface ◽  
Insulin Therapy ◽  
Ldl Receptor ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

scholarly journals Lovastatin Enhances Ecto-5′-Nucleotidase Activity and Cell Surface Expression in Endothelial Cells

2002 ◽  
Vol 90 (4) ◽  
pp. 420-427 ◽  
Author(s):  
S. Ledoux ◽  
D. Laouari ◽  
M. Essig ◽  
I. Runembert ◽  
G. Trugnan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Nucleotidase Activity

scholarly journals Semaphorin 4D inhibits neutrophil activation and is involved in the pathogenesis of neutrophil-mediated autoimmune vasculitis

2017 ◽  
Vol 76 (8) ◽  
pp. 1440-1448 ◽  
Author(s):  
Masayuki Nishide ◽  
Satoshi Nojima ◽  
Daisuke Ito ◽  
Hyota Takamatsu ◽  
Shohei Koyama ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Oxidative Burst ◽  
Serum Levels ◽  
Surface Expression ◽  
Proteolytic Cleavage ◽  
Neutrophil Activation ◽  
Cell Surface Expression ◽  
Human Neutrophils ◽  
Semaphorin 4D

ObjectivesInappropriate activation of neutrophils plays a pathological role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The aim of this study was to investigate the functions of semaphorin 4D (SEMA4D) in regulation of neutrophil activation, and its involvement in AAV pathogenesis.MethodsSerum levels of soluble SEMA4D were evaluated by ELISA. Blood cell-surface expression of membrane SEMA4D was evaluated by flow cytometry. To determine the functional interactions between neutrophil membrane SEMA4D and endothelial plexin B2, wild-type and SEMA4D−/− mice neutrophils were cultured with an endothelial cell line (MS1) stained with SYTOX green, and subjected to neutrophil extracellular trap (NET) formation assays. The efficacy of treating human neutrophils with recombinant plexin B2 was assessed by measuring the kinetic oxidative burst and NET formation assays.ResultsSerum levels of soluble SEMA4D were elevated in patients with AAV and correlated with disease activity scores. Cell-surface expression of SEMA4D was downregulated in neutrophils from patients with AAV, a consequence of proteolytic cleavage of membrane SEMA4D. Soluble SEMA4D exerted pro-inflammatory effects on endothelial cells. Membranous SEMA4D on neutrophils bound to plexin B2 on endothelial cells, and this interaction decreased NET formation. Recombinant plexin B2 suppressed neutrophil Rac1 activation through SEMA4D’s intracellular domain, and inhibited pathogen-induced or ANCA-induced oxidative burst and NET formation.ConclusionsNeutrophil surface SEMA4D functions as a negative regulator of neutrophil activation. Proteolytic cleavage of SEMA4D as observed in patients with AAV may amplify neutrophil-mediated inflammatory responses. SEMA4D is a promising biomarker and potential therapeutic target for AAV.

3-Azido-3-Deoxythymidine Decreases Cell Surface Expression of theα-1,3-Galactosyl Carbohydrate on Porcine Endothelial Cells.

1998 ◽  
Vol 65 (Supplement) ◽  
pp. 260
Author(s):  
J. T. Langell ◽  
G. R. Reiss ◽  
D. V. Cramer ◽  
E. P. Blankenhorn ◽  
J. Y. Kresh
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Porcine Endothelial Cells

Humic Acid Induces Expression of Tissue Factor by Cultured Endothelial Cells: Regulation by Cytosolic Calcium and Protein Kinase C

1994 ◽  
Vol 71 (03) ◽  
pp. 325-330 ◽  
Author(s):  
Hsin-Ling Yang ◽  
Fung-Jou Lu ◽  
Shu-Li Wung ◽  
Hui-Chong Chiu
Keyword(s):  
Endothelial Cells ◽  
Drinking Water ◽  
Protein Kinase C ◽  
Humic Acid ◽  
Protein Kinase ◽  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Vascular Endothelial ◽  
Kinase C

SummaryBlackfoot disease is a thrombotic peripheral vascular disease causally related to the fluorescent humic acid (HA) found in the drinking water of wells in endemic areas in Taiwan. In this study we examined the effect of HA on tissue factor (TF) expression by vascular endothelial cells.Incubation of cultured human umbilical vein endothelial cells (HUVEC) with HA isolated from endemic area drinking water or with a synthetic humic acid polymer (SHA), resulted in enhanced cell surface expression of TF activity by HUVEC. The intracellular calcium level ([Ca24]i) was measured using a calcium-specific fluorescent probe, fura 2. Changes in [Ca24]i level were followed and quantitatively analyzed by spectrofluorometric microscopy, after incubation of the fura 2-loaded HUVEC with HA or SHA in a medium containing 1.8 mM CaCl2. Both HA and SHA increased [Ca2+]i in the presence of extracellular calcium ions, but not in their absence, indicating that influx of extracellular Ca2+ occurred during incubation of HUVEC with HA or SHA. Verapamil, a potent calcium channel blocker, did not abolish the enhancement of [Ca24]i induced by HA or SHA, indicating that specific calcium channels may not be involved in the HA/SHA-induced elevation of [Ca24]i. The elevated [Ca24]i level induced by HA or SHA returned to basal level following removal of HA or SHA and incubation of the washed cells in medium containing 1.8 mM CaCl2. All these changes occurred in the absence of significant cytotoxic effects. The HA/SHA-induced enhancement of cell surface TF activity was inhibited by a specific inhibitor of protein kinase C, H7, suggesting that protein kinase C is involved in the process leading to the enhanced expression of TF activity induced by HA or SHA.In conclusion, this study demonstrates that HA and SHA enhance cell surface expression of TF activity by permeabilization of the cell membrane to extracellular Ca24 ions, leading to elevation of [Ca2+]i that functions as a second messenger to activate protein kinase C, leading finally to enhanced cell surface TF expression. Enhancement of vascular endothelial cell surface TF activity by HA may play a role in the HA-induced thrombotic vascular disorders of Blackfoot disease.

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