scholarly journals Monocyte adhesion to cerebromicrovascular endothelial cells derived from hypertensive and normotensive rats

1994 ◽  
Vol 267 (6) ◽  
pp. H2491-H2497 ◽  
Author(s):  
R. M. McCarron ◽  
L. Wang ◽  
A. L. Siren ◽  
M. Spatz ◽  
J. M. Hallenbeck
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Interleukin 1 ◽  
Intercellular Adhesion Molecule ◽  
Monocyte Adhesion ◽  
Blood Monocytes ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Stroke Risk Factor ◽  
Adhesive Interactions

The stroke risk factor hypertension may function as a predisposing agent by increasing the vulnerability of blood vessels to thrombosis or hemorrhage. The research here demonstrates that cerebrovascular endothelial cells (EC) from spontaneously hypertensive (SHR) and Wistar-Kyoto normotensive (WKY) rats exhibit similar levels of adhesiveness for syngeneic peripheral blood monocytes (e.g., 22.53 +/- 1.32 and 24.35 +/- 1.16%, respectively). Monocyte adhesion to SHR EC was dramatically increased by treatment of EC with lipopolysaccharide, interferon-gamma, or interleukin-1 beta and tumor necrosis factor-alpha (e.g., 106, 68, and 171%, respectively). Identical treatment of WKY EC also increased adhesion albeit at significantly lower levels than observed on concomitantly tested SHR EC (e.g., 47.8, 12.7, and 60.7%, respectively). Allogeneic combinations of monocytes and EC again demonstrated significantly more upregulation of adhesion by treatment of SHR EC than WKY EC. Characterization of these adhesive interactions revealed the interplay of adhesion pathways, which include lymphocyte functional antigen-1/intercellular adhesion molecule-1 (ICAM-1), Mac-1/ICAM-1, and very late activation antigen-4/vascular adhesion molecule-1 as well as other undetermined mechanisms. In summary, these findings indicate hypertension may enhance responsiveness of endothelium to factors that promote monocyte adhesion.

scholarly journals Insulin and Insulin-Like Growth Factor-I Receptors Differentially Mediate Insulin-Stimulated Adhesion Molecule Production by Endothelial Cells

Endocrinology ◽  
2009 ◽  
Vol 150 (8) ◽  
pp. 3475-3482 ◽  
Author(s):  
Guolian Li ◽  
Eugene J. Barrett ◽  
Seung-Hyun Ko ◽  
Wenhong Cao ◽  
Zhenqi Liu
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Small Interfering Rna ◽  
Receptor Activation ◽  
Intercellular Adhesion Molecule ◽  
Monocyte Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Igf I ◽  
Interfering Rna

Patients with type 2 diabetes are hyperinsulinemic and insulin resistant and develop premature atherosclerosis. High concentrations of insulin stimulate the production of adhesion molecules by endothelial cells (ECs). ECs express abundant IGF-I receptors as well as insulin receptors. Whether IGF-I receptors contribute to insulin-induced endothelial production of adhesion molecules is unknown. Bovine aortic ECs (BAECs) were incubated with insulin (100 nm) for 24 h. The cellular content of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) was measured, and monocyte adhesion to ECs was quantified. Insulin increased both VCAM-1 (P < 0.001) and ICAM-1 (P < 0.0002) content, which was accompanied by an increased number of monocytes adherent to BAECs (P = 0.0001). Inhibition of either MAPK kinase-1 or p38 MAPK but not phosphatidylinositol 3-kinase abolished insulin-mediated production of adhesion molecules. Insulin receptor small interfering RNA knockdown abolished insulin-stimulated increases of ICAM-1 but not VCAM-1. Conversely, IGF-I receptor blockade with either a neutralizing antibody or specific small interfering RNA eliminated insulin-induced VCAM-1 but not ICAM-1 production. Blockade of signaling via either the insulin or IGF-I receptors decreased monocyte adherence to BAECs (P < 0.01 for each). We conclude that insulin and IGF-I receptors differentially mediate the production of adhesion molecules by ECs and monocyte adhesion onto the vascular endothelium in response to the hyperinsulinemic state. Dual-receptor activation may most effectively contribute to the pathogenesis of atherosclerotic disease in diabetes.

scholarly journals KRIT1 Deficiency Promotes Aortic Endothelial Dysfunction

2019 ◽  
Vol 20 (19) ◽  
pp. 4930 ◽  
Author(s):  
Francesco Vieceli Dalla Sega ◽  
Raffaella Mastrocola ◽  
Giorgio Aquila ◽  
Francesca Fortini ◽  
Claudia Fornelli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Loss Of Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Aortic Endothelial

Loss-of-function mutations of the gene encoding Krev interaction trapped protein 1 (KRIT1) are associated with the pathogenesis of Cerebral Cavernous Malformation (CCM), a major cerebrovascular disease characterized by abnormally enlarged and leaky capillaries and affecting 0.5% of the human population. However, growing evidence demonstrates that KRIT1 is implicated in the modulation of major redox-sensitive signaling pathways and mechanisms involved in adaptive responses to oxidative stress and inflammation, suggesting that its loss-of-function mutations may have pathological effects not limited to CCM disease. The aim of this study was to address whether KRIT1 loss-of-function predisposes to the development of pathological conditions associated with enhanced endothelial cell susceptibility to oxidative stress and inflammation, such as arterial endothelial dysfunction (ED) and atherosclerosis. Silencing of KRIT1 in human aortic endothelial cells (HAECs), coronary artery endothelial cells (HCAECs), and umbilical vein endothelial cells (HUVECs) resulted in increased expression of endothelial proinflammatory adhesion molecules vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) and in enhanced susceptibility to tumor necrosis factor alpha (TNF-α)-induced apoptosis. These effects were associated with a downregulation of Notch1 activation that could be rescued by antioxidant treatment, suggesting that they are consequent to altered intracellular redox homeostasis induced by KRIT1 loss-of-function. Furthermore, analysis of the aorta of heterozygous KRIT1+/− mice fed a high-fructose diet to induce systemic oxidative stress and inflammation demonstrated a 1.6-fold increased expression of VCAM-1 and an approximately 2-fold enhanced fat accumulation (7.5% vs 3.6%) in atherosclerosis-prone regions, including the aortic arch and aortic root, as compared to corresponding wild-type littermates. In conclusion, we found that KRIT1 deficiency promotes ED, suggesting that, besides CCM, KRIT1 may be implicated in genetic susceptibility to the development of atherosclerotic lesions.

XO increases neutrophil adherence to endothelial cells by a dual ICAM-1 and P-selectin-mediated mechanism

1997 ◽  
Vol 82 (3) ◽  
pp. 866-873 ◽  
Author(s):  
Lance S. Terada ◽  
Brooks M. Hybertson ◽  
Kevin G. Connelly ◽  
David Weill ◽  
Dale Piermattei ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Platelet Activating Factor ◽  
Surface Expression ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Neutrophil Adherence ◽  
Adhesive Interactions ◽  
Static Conditions

Terada, Lance S., Brooks M. Hybertson, Kevin G. Connelly, David Weill, Dale Piermattei, and John E. Repine. XO increases neutrophil adherence to endothelial cells by a dual ICAM-1 and P-selectin-mediated mechanism. J. Appl. Physiol. 82(3): 866–873, 1997.—Circulating xanthine oxidase (XO) can modify adhesive interactions between neutrophils and the vascular endothelium, although the mechanisms underlying this effect are not clear. We found that treatment with XO of bovine pulmonary artery endothelial cells (EC), but not neutrophils or plasma, increased adherence, suggesting that XO had its primary effect on EC. The mechanism by which XO increased neutrophil adherence to EC involved binding of XO to EC and production of H2O2. XO also increased platelet-activating factor production by EC by a H2O2-dependent mechanism. Similarly, the platelet-activating factor-receptor antagonist WEB-2086 completely blocked XO-mediated neutrophil EC adherence. In addition, neutrophil adherence was dependent on the β2-integrin Mac-1 (CD11b/CD18) but not on leukocyte functional antigen-1 (CD11a/CD18). Treatment of EC with XO for 30 min did not alter intercellular adhesion molecule-1 surface expression but increased expression of P-selectin and release of von Willibrand factor. Antibodies against P-selectin (CD62) did not affect XO-mediated neutrophil adherence under static conditions but decreased both rolling and firm adhesive interactions under conditions of shear. We conclude that extracellular XO associates with the endothelium and promotes neutrophil-endothelial cell interactions through dual intercellular adhesion molecule-1 and P-selectin ligation, by a mechanism that involves platelet-activating factor and H2O2as intermediates.

Differential monocyte adhesion and adhesion molecule expression in venous and arterial endothelial cells

1999 ◽  
Vol 276 (1) ◽  
pp. L9-L19 ◽  
Author(s):  
Theodore J. Kalogeris ◽  
Christopher G. Kevil ◽  
F. Stephen Laroux ◽  
Laura L. Coe ◽  
Travis J. Phifer ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Interleukin 1 ◽  
Surface Expression ◽  
Nuclear Factor Κb ◽  
Intercellular Adhesion Molecule ◽  
Nuclear Factor ◽  
Adhesion Molecule Expression ◽  
Intercellular Adhesion Molecule 1

We compared U-937 cell adhesion and adhesion molecule expression in human umbilical venous (HUVECs) and arterial (HUAECs) endothelial cells exposed to tumor necrosis factor (TNF), interleukin-1, and lipopolysaccharide (LPS). TNF and LPS stimulated vascular cell adhesion molecule (VCAM)-1 surface expression and adhesion of U-937 monocyte-like cells to HUVECs but not to HUAECs. Antibody studies demonstrated that in HUVECs at least 75% of the adhesion response is VCAM-1 mediated. Interleukin-1 stimulated U-937 cell adhesion to and VCAM-1 surface expression in both HUVECs and HUAECs. Pyrrolidinedithiocarbamate and the proteasome inhibitor MG-132 blocked TNF- and LPS-stimulated U-937 cell adhesion to HUVECs. These agents also significantly decreased TNF- and LPS-stimulated increases in HUVEC surface VCAM-1. TNF increased VCAM-1 protein and mRNA in HUVECs that was blocked by pyrrolidinedithiocarbamate. However, neither TNF or LPS stimulated VCAM-1 expression in HUAECs. TNF stimulated expression of both intercellular adhesion molecule-1 and E-selectin in HUVECs, but in HUAECs, only intercellular adhesion molecule-1 was increased. Electrophoretic mobility shift assays demonstrated no difference in the pattern of TNF-stimulated nuclear factor-κB activation between HUVECs and HUAECs. These studies demonstrate a novel and striking insensitivity of arterial endothelium to the effects of TNF and LPS and indicate a dissociation between the ability of HUAECs to upregulate nuclear factor-κB and VCAM-1.

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