Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The specificity of monoclonal antibody 10F3, generated to smooth muscle cells isolated from fetal human aorta, has been further explored in a series of biological, biochemical, and immunocytochemical studies. In the first assay, it was found that 10F3 could inhibit aggregation of phytohemagglutinin (PHA)-induced lymphocytes in a manner comparable to that of antibody RR1/1, an anti-intercellular adhesion molecule 1 (ICAM-1) monoclonal antibody. In immunoprecipitation experiments followed by one-dimensional gel electrophoresis, both 10F3 and RR1/1 immunoprecipitated 90 kd proteins, with results suggesting that the two antibodies recognized different epitopes of the same molecule. A series of immunocytochemical studies on human atherosclerotic lesions was performed; using single-labeling techniques, 10F3-positive cells were found in the vessel wall and in lesions of virtually all specimens of fatty streaks and fibrous plaques. Using double-labeling techniques, 10F3-positive macrophages and 10F3-positive smooth muscle cells were found; however, there were also a significant number of non-smooth muscle, nonmacrophage 10F3-positive cells. These studies demonstrate that 10F3 identifies ICAM-1, and that this protein is expressed on a variety of cell types in human atherosclerotic lesions. ICAM-1 may represent a developmentally regulated protein that is expressed in fetal but not adult mesenchymal cells, but can be re-expressed in pathologic processes such as atherosclerosis.
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PMID:Various cell types in human atherosclerotic lesions express ICAM-1. Further immunocytochemical and immunochemical studies employing monoclonal antibody 10F3. 134 6

There is evidence that vascular endothelium directs the accumulation of leukocytes in inflammation through various means, particularly by the expression of specific cell surface molecules which are adhesive for ligands on circulating leukocytes. Examples of such molecules are E-selectin and intercellular adhesion molecule 1 (ICAM-1). In an experimental model of various forms of inflammation, E-selectin and ICAM-I were induced in association with adhesion and emigration of circulating polymorphonuclear and mononuclear leukocytes. Further work in humans showed endothelium to express E-selectin in inflammation. In addition, the presence of a leukocyte ligand for E-selectin, sialyl-Lewis X, has been seen on cells accumulating in inflammation. Furthermore, sialyl-Lewis X was also unexpectedly seen on endothelium. The role of sialyl-Lewis X on endothelium is as yet uncertain, although it may function as an adhesion receptor for leukocytes. Other endothelial adhesion receptors, such as vascular cell adhesion molecule 1 (VCAM-1), are described. Atherosclerosis shows many features in common with inflammation. These are discussed, and the demonstrated and potential relevance of endothelial adhesive phenomena in routine inflammation to those in atherosclerosis are reviewed. For example, a VCAM-1 homologue has been described on the endothelium over evolving atherosclerotic lesions in rabbits.
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PMID:Endothelial-leukocyte adhesive interactions in inflammatory diseases. 751 Jun 38

The rate of atherosclerosis is accelerated in humans with diabetes. The adhesion of monocytes to the vascular endothelium is a key event in the development of atherosclerosis. Alloxan (ALX)-induced diabetes in rabbits causes leukocyte accumulation on the arterial surface. However, the effect of glucose exposure on monocyte binding is not understood. We evaluated the effect of chronic elevated glucose on human monocyte binding to human aortic endothelial cells (HAEC) in culture. Monocyte binding to HAEC was significantly increased by chronic incubation of HAEC in high glucose for 7-10 days (CH-HG; 25 mM) compared with cells cultured for the same time in normal glucose (5.5 mM; CH-HG, 188 +/- 10 cells/field vs. normal glucose, 111 +/- 7; P < 0.0005). Use of mannitol at a concentration to stimulate the hyperosmolar effects of glucose did not significantly alter monocyte binding. Acute 20-min exposure of HAEC to high glucose did not alter monocyte binding. The adherence of HL-60 cells, a neutrophil-like cell line, or human neutrophils was not induced by CH-HG culture. High glucose-induced monocyte binding was not associated with induction of the major endothelial cell adhesion molecules, including E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 (ICAM-1). A monoclonal antibody TS1-18 to the beta 2 integrin component that is involved in binding to ICAM-1 on endothelial cells significantly reduced monocyte binding, whereas anti-VLA-4 antibody was not effective. These results suggest that hyperglycemia can accelerate the rate of atherosclerosis in diabetics by increasing monocyte binding to the endothelium.
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PMID:Evidence that glucose increases monocyte binding to human aortic endothelial cells. 752 Aug 76

Increased expression of cell adhesion molecules is an important pathological event during the development of atherosclerosis. The smooth muscle cell (SMC) is one of the cell types present in the atherosclerotic lesion. To evaluate the regulation of adhesion molecules in human vascular SMCs and its possible role, we studied the expression of adhesion molecules in SMCs stimulated with interleukin 1-beta (IL-1 beta), a pleiotropic cytokine that is involved in the pathological development of vascular diseases including atherosclerosis and restenosis. Our data demonstrated that IL-1 beta markedly induced the adhesiveness of human vascular SMCs for monocytes and neutrophils in a concentration (10 pM - 10 nM)- and time (0.5-24 h)-dependent manner. The maximal induced adhesion by IL-1 beta (1 nM) was reached at 4 h, with 4.6-fold and 3.3-fold for monocytes and neutrophils, respectively. This induction was dose-dependently inhibited by the IL-1 receptor antagonist (IL-1 ra). The IL-1 beta-induced expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin 1 (ELAM-1) on SMCs was examined by reverse transcription/polymerase chain reaction (RT/PCR). Unstimulated, serum-deprived SMCs expressed a low or undetectable level of mRNA for these adhesion molecules. The expression of ICAM-1 and VCAM-1 but not ELAM-1 mRNA was significantly induced with IL-1 beta in a concentration (1 fM - 1 nM)- and time (0.5 - 24 h)-dependent manner. The maximal increase in ICAM-1 and VCAM-1 mRNAs was reached at 4 h after IL-1 beta stimulation. The IL-1 beta-induced adhesion of SMCs for monocytes was partially inhibited by monoclonal anti-human ICAM-1 and anti-human VCAM-1 antibody, but not by anti-human ELAM-1 antibody. Pretreatment of monocytes with anti-human integrin beta 2 antibody significantly reduced the adhesion of monocytes to IL-1 beta-stimulated SMCs. These results suggest that IL-1 beta is a potent inducer for ICAM-1 and VCAM-1 expression in human vascular SMC, and could play a role in the pathogenesis of atherosclerosis by recruitment and retention of inflammatory cells such as monocytes and neutrophils in the lesions.
Atherosclerosis 1995 May
PMID:Interleukin-1 beta induces expression of adhesion molecules in human vascular smooth muscle cells and enhances adhesion of leukocytes to smooth muscle cells. 754 98

Although primarily recognized for its role in hemostasis, fibrinogen is also required for competent inflammatory reactions in vivo. It is now shown that fibrinogen promotes adhesion to and migration across an endothelial monolayer of terminally differentiated myelomonocytic cells. This process does not require chemotactic/haptotactic gradients or cytokine stimulation of the endothelium and is specific for the association of fibrinogen with intercellular adhesion molecule 1 (ICAM-1) on endothelium. Among other adhesive plasma proteins, fibronectin fails to increase the binding of leukocytes to endothelium, or transendothelial migration, whereas vitronectin promotes the binding but not the migration. The fibrinogen-mediated leukocyte adhesion and transendothelial migration could be inhibited by a peptide from the fibrinogen gamma-chain sequence N117NQKIVNL-KEKVAQLEA133, which blocks the binding of fibrinogen to ICAM-1. This interaction could also be inhibited by new anti-ICAM-1 monoclonal antibodies that did not affect the ICAM-1-CD11a/CD18 recognition, thus suggesting that the fibrinogen binding site on ICAM-1 may be structurally distinct from regions previously implicated in leukocyte-endothelium interaction. Therefore, binding of fibrinogen to vascular cell receptors is sufficient to initiate (i) increased leukocyte adhesion to endothelium and (ii) leukocyte transendothelial migration. These two processes are the earliest events of immune inflammatory responses and may also contribute to atherosclerosis.
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PMID:Regulation of leukocyte-endothelium interaction and leukocyte transendothelial migration by intercellular adhesion molecule 1-fibrinogen recognition. 787 9

Gene targeting was used to produce mice deficient in intercellular adhesion molecule 1 (ICAM-1) or CD54, an immunoglobulin-like cell adhesion molecule that binds beta 2 integrins. Homozygous deficient animals develop normally, are fertile, and have a moderate granulocytosis. The nature of the mutation, RNA analysis, and immunostaining are consistent with complete loss of surface expression of ICAM-1. Deficient mice exhibit prominent abnormalities of inflammatory responses including impaired neutrophil emigration in response to chemical peritonitis and decreased contact hypersensitivity to 2,4-dinitrofluorobenzene. Mutant cells provided negligible stimulation in the mixed lymphocyte reaction, although they proliferated normally as responder cells. These mutant animals will be extremely valuable for examining the role of ICAM-1 and its counterreceptors in inflammatory disease processes and atherosclerosis.
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PMID:Inflammatory and immune responses are impaired in mice deficient in intercellular adhesion molecule 1. 810 38

To clarify the etiology of accelerated atherosclerosis in patients with diabetes mellitus, we measured expression of intercellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1), and E-selection on the cell surface by enzyme-linked immunosorbent assay and ICAM-1 mRNA content in human umbilical vein endothelial cells exposed to 5.5 mM glucose (NG), 33 mM glucose (HG), or 27.5 mM mannitol plus 5.5 mM glucose (HM).1) Cell-surface ICAM-1 expression in HG and HM cells was maximally increased by 37% and 32% (P < 0.01), respectively. This effect was dependent on glucose concentration in the medium and was found as early as 24 h and maintained until 6 days after exposing cells of HG. However, neither VCAM-1 nor E-selection expression were affected by HG conditions. 2) Both HG and HM induced increased mRNA content between 6 and 12 h after the stimulation. 3) Adhesion of THP-1 cells to endothelial cells exposed to HG and HM was increased, when compared to NG conditions. These results indicate that osmotic effects can induce increased mRNA and cell-surface expression of ICAM-1 via an as yet unknown mechanism.
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PMID:Expression of intercellular adhesion molecules 1 (ICAM-1) via an osmotic effect in human umbilical vein endothelial cells exposed to high glucose medium. 863 95

Cigarette smoking is clearly linked with increased incidence of atherosclerosis and cardiovascular disease. The adherence of blood monocytes to the endothelium, followed by their migration beneath the endothelium, are initiating events in the formation of foam cells, promoting atherogenesis. We show that cigarette smoke condensate (CSC)-induced surface expression of a subset of cell adhesion molecules (CAM) [intercellular adhesion molecule 1 (ICAM-1), endothelial leukocyte adhesion molecule 1 (ELAM-1), and vascular cell adhesion molecule 1 (VCAM-1)] in human umbilical vein endothelial cells (HUVEC) is associated with an increase in the binding activity of nuclear transcription factor NF-kappa B to the consensus motif common to the CAM genes. Furthermore, CSC (25 microgram/ml) both increases the rate of transendothelial migration of vitamin D3-differentiated monocyte-like cells across the HUVEC monolayer by 200% and causes an approximately 10-fold increases in the phosphorylation of platelet endothelial CAM (PECAM-1), an adhesion molecule located at intercellular junctions and involved in endothelial cell-cell adhesion. Our results show that CSC-induced activation of protein kinase C in endothelial cells initiates a signaling pathways, leading to heightened binding of NF-kappa B to specific DNA sequences, which in turn increases surface expression of the subset of CAMs. Furthermore, our studies demonstrate a link between the phosphorylation of PECAM-1 and the migration of blood monocytes across vascular endothelium.
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PMID:Cigarette smoke condensate-induced adhesion molecule expression and transendothelial migration of monocytes. 892 67

The effect of aminoguanidine (AG) on the expression of adhesion molecules on nonactivated human umbilical vein endothelial cells (HUVEC) was investigated in vitro. Nonactivated HUVEC cultivated on long-term glycated fibronectin (FN) as compared to native FN showed a significant upregulation of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and CD31 which could be further promoted by long-term glycated bovine serum albumin. AG, at a concentration of 0.01 mol/l, caused an upregulation of ICAM-1 of 48 +/- 17.4% in HUVEC cultivated on gelatin. In contrast, VCAM-1 and E-selectin remained unaffected. At this concentration, formation of advanced glycation end products (AGE) was inhibited by 57%, as determined immunologically, and by 50%, as verified by AGE-specific fluorescence. A hypothesis concerning the upregulation of ICAM-1 by AG as compared to VCAM-1 is proposed relating to its relative redox insensitivity. Our results demonstrate that the beneficial effect of AG in reducing the risk of accelerated development of atherosclerosis in diabetic patients by inhibiting formation of AGE on matrix proteins such as FN might be hampered by its tendency to upregulate ICAM-1 on endothelial cells.
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PMID:Effects of aminoguanidine on adhesion molecule expression of human endothelial cells. 934 1

Consumption of diets rich in monounsaturated fatty acids (MUFAs) has been linked with a low prevalence of atherosclerosis and there has been great interest in the effects of MUFAs on lipoprotein metabolism. Less attention has been paid to the effects of MUFAs on the immune system, yet cells of the immune system are an inherent part of the inflammatory events involved in atherosclerosis and several animal studies showed that olive oil has some potent immunomodulatory actions. We therefore considered it important to investigate the effects of chronic consumption of MUFAs on several immune cell functions in healthy humans. Healthy middle-aged males entered a double-blind, randomized, controlled trial in which they consumed either a MUFA diet or a control diet for 2 mo. There was a significant decrease in the expression of intercellular adhesion molecule 1 by peripheral blood mononuclear cells from subjects consuming the MUFA diet. Consumption of the MUFA diet did not affect natural killer cell activity or proliferation of mitogen-stimulated leukocytes. The effects of a MUFA-rich diet on adhesion molecule expression may have implications for the influence of dietary fat on inflammatory diseases, including atherosclerosis.
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PMID:Effect of olive oil on immune function in middle-aged men. 944 Mar 87


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