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 Differential Signal Transduction of Progesterone and Medroxyprogesterone Acetate in Human Endothelial Cells

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5745-5756 ◽  
Author(s):  
Tommaso Simoncini ◽  
Paolo Mannella ◽  
Letizia Fornari ◽  
Antonella Caruso ◽  
Monica Y. Willis ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Endothelial Cells ◽  
Glucocorticoid Receptor ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Medroxyprogesterone Acetate ◽  
Intercellular Adhesion Molecule ◽  
Human Endothelial Cells ◽  
Intercellular Adhesion Molecule 1

Abstract The conjugated equine estrogens-only arm of the Women’s Health Initiative trial, showing a trend toward protection from heart disease as opposed to women receiving also medroxyprogesterone acetate (MPA), strengthens the debate on the cardiovascular effects of progestins. We compared the effects of progesterone (P) or MPA on the synthesis of nitric oxide and on the expression of leukocyte adhesion molecules, characterizing the signaling events recruited by these compounds. Although P significantly increases nitric oxide synthesis via transcriptional and nontranscriptional mechanisms, MPA is devoid of such effects. Moreover, when used together with physiological estradiol (E2) concentrations, P potentiates E2 effects, whereas MPA impairs E2 signaling. These findings are observed both in isolated human endothelial cells as well as in vivo, in ovariectomized rat aortas. A marked difference in the recruitment of MAPK and phosphatidylinositol-3 kinase explains the divergent effects of the two gestagens. In addition, both P and MPA decrease the adhesiveness of endothelial cells for leukocytes when given alone or with estrogen. MPA is more potent than P in inhibiting the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. However, when administered together with physiological amounts of glucocorticoids, MPA (which also binds glucocorticoid receptor) markedly interferes with the hydrocortisone-dependent stabilization of the transcription factor nuclear factor κB and with the expression of adhesion molecules, acting as a partial glucocorticoid receptor antagonist. Our findings show significant differences in the signal transduction pathways recruited by P and MPA in endothelial cells, which may have relevant clinical implications.

scholarly journals The Cytolytically Inactive Terminal Complement Complex Activates Endothelial Cells to Express Adhesion Molecules and Tissue Factor Procoagulant Activity

1997 ◽  
Vol 185 (9) ◽  
pp. 1619-1628 ◽  
Author(s):  
Francesco Tedesco ◽  
Mario Pausa ◽  
Ermanno Nardon ◽  
Martino Introna ◽  
Alberto Mantovani ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tissue Factor ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Membrane Attack Complex ◽  
Procoagulant Activity ◽  
Biologically Active ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1

The membrane attack complex of complement (C) in sublytic concentrations stimulates endothelial cells (EC) to express adhesion molecules and to release biologically active products. We have examined the ability of a cytolytically inactive form of this complex, which is incapable of inserting into the cell membrane, to upregulate the expression of adhesion molecules and of tissue factor (TF) procoagulant activity. The inactive terminal C complex (iTCC) was prepared by mixing C5b6, C7, C8, and C9 and was purified by fast protein liquid chromatography on a Superose 12 column. Binding of this complex to EC was found to be dose dependent and was inhibited by anti-C9 antibodies, as assessed both by ELISA using an mAb anti-C9 neoantigen and by measuring cell-bound 125I-labeled iTCC. Exposure of EC to iTCC resulted in a dose- and time-dependent expression of endothelial leukocyte adhesion molecule 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 accompanied by increased levels of the corresponding mRNA, but not in the rapid expression of P-selectin. Inactive TCC also induced increased TF activity evaluated by a chromogenic assay that measures the formation of factor Xa. These effects were inhibited by anti-C9 antibodies. The data support the conclusion that iTCC may induce proinflammatory and procoagulant activities on EC.

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.

Synergism of multiple adhesion molecules in mediating cytoadherence of Plasmodium falciparum–infected erythrocytes to microvascular endothelial cells under flow

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2292-2298 ◽  
Author(s):  
Bryan G. Yipp ◽  
Samantha Anand ◽  
Tineke Schollaardt ◽  
Kamala D. Patel ◽  
Sornchai Looareesuwan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasmodium Falciparum ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Oncostatin M ◽  
Intercellular Adhesion Molecule ◽  
Microvascular Endothelial Cells ◽  
Intercellular Adhesion Molecule 1 ◽  
Microvascular Endothelium ◽  
Microvascular Endothelial

Plasmodium falciparum–infected erythrocytes (IRBCs) have been shown to interact with a number of endothelial adhesion molecules expressed on transfectants, on cell lines, and as immobilized purified receptor proteins under flow conditions. However, the experiments were designed in such a way that maximal numbers of adhesion molecules were provided as substratum. Whether the interactive events actually occur on microvascular endothelium, where the distribution and expression of adhesion molecules may be less, remains undetermined. In this study, the cytoadherance of IRBCs on human dermal microvascular endothelial cells (HDMECs) as a model of human microvasculature was examined. IRBCs were observed to tether, roll, and adhere on resting HDMECs, which constitutively expressed CD36 and intercellular adhesion molecule-1 (ICAM-1) at an optimal shear stress of 1 dyne/cm2. Stimulation of HDMECs with tumor necrosis factor–α for 5 and 24 hours, which resulted in up-regulation of ICAM-1 and induction of vascular cell adhesion molecule-1 expression, significantly increased the percentage of rolling cells that adhered without affecting the rolling flux. In contrast, P-selectin expression on HDMECs induced by oncostatin M led to an increase in both rolling flux and adhesion. Inhibition studies with receptor-specific monoclonal antibodies revealed that adhesion of IRBCs on HDMECs was largely CD36 dependent, whereas rolling could be mediated by any of the adhesion molecules studied. Collectively, these findings indicate that IRBCs interact synergistically with multiple adhesion molecules on vascular endothelium. The rolling of IRBCs may be the rate-limiting step in cytoadherance, since it can be modulated by cytokines to enhance CD36-mediated IRBC adhesion.

Synergism of multiple adhesion molecules in mediating cytoadherence of Plasmodium falciparum–infected erythrocytes to microvascular endothelial cells under flow

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2292-2298 ◽  
Author(s):  
Bryan G. Yipp ◽  
Samantha Anand ◽  
Tineke Schollaardt ◽  
Kamala D. Patel ◽  
Sornchai Looareesuwan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasmodium Falciparum ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Oncostatin M ◽  
Intercellular Adhesion Molecule ◽  
Microvascular Endothelial Cells ◽  
Intercellular Adhesion Molecule 1 ◽  
Microvascular Endothelium ◽  
Microvascular Endothelial

Abstract Plasmodium falciparum–infected erythrocytes (IRBCs) have been shown to interact with a number of endothelial adhesion molecules expressed on transfectants, on cell lines, and as immobilized purified receptor proteins under flow conditions. However, the experiments were designed in such a way that maximal numbers of adhesion molecules were provided as substratum. Whether the interactive events actually occur on microvascular endothelium, where the distribution and expression of adhesion molecules may be less, remains undetermined. In this study, the cytoadherance of IRBCs on human dermal microvascular endothelial cells (HDMECs) as a model of human microvasculature was examined. IRBCs were observed to tether, roll, and adhere on resting HDMECs, which constitutively expressed CD36 and intercellular adhesion molecule-1 (ICAM-1) at an optimal shear stress of 1 dyne/cm2. Stimulation of HDMECs with tumor necrosis factor–α for 5 and 24 hours, which resulted in up-regulation of ICAM-1 and induction of vascular cell adhesion molecule-1 expression, significantly increased the percentage of rolling cells that adhered without affecting the rolling flux. In contrast, P-selectin expression on HDMECs induced by oncostatin M led to an increase in both rolling flux and adhesion. Inhibition studies with receptor-specific monoclonal antibodies revealed that adhesion of IRBCs on HDMECs was largely CD36 dependent, whereas rolling could be mediated by any of the adhesion molecules studied. Collectively, these findings indicate that IRBCs interact synergistically with multiple adhesion molecules on vascular endothelium. The rolling of IRBCs may be the rate-limiting step in cytoadherance, since it can be modulated by cytokines to enhance CD36-mediated IRBC adhesion.

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