UMLS:C0004153 - FACTA Search

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Query: UMLS:C0004153 (atherosclerosis)
77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Induction of endothelial adhesion molecules by the cytokine tumor necrosis factor-alpha (TNF) can occur independently of protein kinase C and activation of a protein tyrosine kinase (PTK) has recently been implicated in the upregulation of vascular cell adhesion molecule 1 (VCAM-1) by interleukin-4 (IL-4) on endothelial cells. We demonstrate that the PTK inhibitors herbimycin A or genistein suppress induction of endothelial VCAM-1 and E-selectin, as well as subsequent monocytic cell adhesion to endothelial cells stimulated by TNF. Inhibition studies indicate that specific tyrosine phosphorylation following PTK activation is involved in the mobilization of the transcription factor, nuclear factor kappa B, and VCAM-1 mRNA expression. This may have implications for pathophysiological conditions that involve the upregulation of these molecules (e.g. inflammation and atherosclerosis).
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PMID:Involvement of tyrosine phosphorylation in endothelial adhesion molecule induction. 873 63

Decreased nitric oxide (NO) activity, the formation of reactive oxygen species, and increased endothelial expression of the redox-sensitive vascular cell adhesion molecule 1 (VCAM-1) gene in the vessel wall are early and characteristic features of atherosclerosis. To explore whether these phenomena are functionally interrelated, we tested the hypothesis that redox-sensitive VCAM-1 gene expression is regulated by a NO-sensitive mechanism. In early passaged human umbilical vein endothelial cells and human dermal microvascular endothelial cells, the NO donor diethylamine-NO (DETA-NO, 100 microM) reduced VCAM-1 gene expression induced by the cytokine tumor necrosis factor alpha (TNF-alpha, 100 units/ml) at the cell surface level by 65% and intracellular adhesion molecule 1 (ICAM-1) gene expression by 35%. E-selectin gene expression was not affected. No effect on expression of cell adhesion molecules was observed with DETA alone. Moreover, DETA-NO suppressed TNF-alpha-induced mRNA accumulation of VCAM-1 and TNF-alpha-mediated transcriptional activation of the human VCAM-1 promoter. Conversely, treatment with NG-monomethyl-L-arginine (L-NMMA, 1 mM), an inhibitor of NO synthesis, augmented cytokine induction of VCAM-1 and ICAM-1 mRNA accumulation. By gel mobility shift analysis, DETA-NO inhibited TNF-alpha activation of DNA binding protein activity to the VCAM-1 NF-kappa B like binding sites. Peroxy-fatty acids such as 13-hydroperoxydodecanoeic acid (linoleyl hydroperoxide) may serve as an intracellular signal for NF-kappa B activation. Using thin layer chromatography, DETA-NO (100 microM) suppressed formation of this metabolite, suggesting that DETA-NO modifies the reactivity of oxygen intermediates in the vascular endothelium. Through this mechanism, NO may function as an immunomodulator of the vessel wall and thus mediate inflammatory events involved in the pathogenesis of atherosclerosis.
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PMID:Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells. 879 63

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

Lp(a) is a major inherited risk factor for premature atherosclerosis. The mechanism of Lp(a) atherogenicity has not been elucidated, but likely involves both its ability to interfere with plasminogen activation and its atherogenic potential as a lipoprotein particle after receptor-mediated uptake. We demonstrate that Lp(a) stimulates production of vascular cell adhesion molecule 1 (VCAM-1) and E-selectin in cultured human coronary artery endothelial cells (HCAEC). This effect resulted from a rise in intracellular free calcium induced by Lp(a) and could be inhibited by the intracellular calcium chelator, BAPTA/AM. The involvement of the LDL and VLDL receptors in Lp(a) activation of HCAEC were ruled out since Lp(a) induction of adhesion molecules was not prevented by an antibody (IgGC7) to the LDL receptor or by receptor-activating protein, an antagonist of ligand binding to the VLDL receptor. Addition of alpha2-macroglobulin as well as treatment with heparinase, chondroitinase ABC, and sodium chlorate did not decrease levels of VCAM-1 and E-selectin stimulated by Lp(a), suggesting that neither the low density lipoprotein receptor-related protein nor cell-surface proteoglycans are involved in Lp(a)-induced adhesion molecule production. Neither does the binding site on HCAEC responsible for adhesion molecule production by Lp(a) appear to involve plasminogen receptors, as levels of VCAM-1 and E-selectin were not significantly decreased by the addition of glu-plasminogen, the lysine analog epsilon-aminocaproic acid, or by trans-4-(aminomethyl)-cyclohexanecarboxymethylic acid (tranexamic acid), which acts by binding to the lysine binding sites carried on the kringle structures in plasminogen. In contrast, recombinant apolipoprotein (a) [r-apo(a)] competed with Lp(a) and attenuated the expression of VCAM-1 and E-selectin. In summary, we have identified a calcium-dependent interaction of Lp(a) with HCAEC capable of inducing potent surface expression of VCAM-1 and E-selectin that does not appear to involve any of the known potential Lp(a) binding sites. Because leukocyte recruitment to the vessel wall appears to represent one of the important early events in atherogenesis, this newly described endothelial cell-activating effect of Lp(a) places it at a crucial juncture in the initiation of atherogenic disease and may lead to a better understanding of the role of Lp(a) in the vascular biology of atherosclerosis.
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PMID:Expression of adhesion molecules by lp(a): a potential novel mechanism for its atherogenicity. 983 67

Activation of human, arterial endothelial cells (ECs) is an early event in the pathogenesis of atherosclerosis. To identify the repertoire of genes that are differentially expressed after activation, we used serial analysis of gene expression (SAGE) to compare the mRNA spectrum of quiescent ECs with that of ECs activated for 6h with a strong atherogenic stimulus. SAGE methodology generates concatenated 'tags' of 10bp that are derived from a specific mRNA. About 5% of over 12000 tags analyzed is derived from genes that are differentially expressed (at least 5-fold up- or downregulated). These transcript tags are derived from only 56 genes, close to 1% of the total number of analyzed genes. Among these 56 differentially expressed genes are 42 known genes, including the hallmark endothelial cell activation markers interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), plasminogen activator inhibitor 1 (PAI-1), Gro-alpha, Gro-beta and E-selectin. Differential transcription of a selection of the upregulated genes was confirmed by Northern blot analysis. A novel observation is the upregulation of activin betaA mRNA, a member of the transforming growth factor beta family. Apparent discrepancies between this novel technology and conventional methods are discussed. In conclusion, we demonstrate that for the application of SAGE, a moderate number of analyzed transcript tags suffices to reveal the significant alterations of EC transcription that results from a strong atherogenic stimulus.
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PMID:Serial analysis of gene expression to assess the endothelial cell response to an atherogenic stimulus. 988 96

Adhesion molecules on the endothelial cell membrane play an important role in the pathogenesis of atherosclerosis. Levels of soluble forms of cell adhesion molecules are reportedly elevated in patients with peripheral artery vessel disease and in patients with an atherosclerotic aorta. The present study investigated the association of serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), and soluble P-selectin (sP-selectin) with coronary heart disease (CHD) and the extent of coronary atherosclerosis, and examined the influence of serum levels of lipids, lipoproteins and apolipoproteins (apo) in subjects with (n=52, M/F:43/9) and without (controls, n=40, M/F:25/15) angiographically proven coronary atherosclerosis. After controlling for age and gender, levels of sVCAM-1 (least squares mean +/- std error: 565+/-36 ng/ml vs 540+/-41 ng/ml, ns), sICAM-1 (261+/-17ng/ml vs 247+/-19ng/ml, ns), and sP-selectin (142+/-8ng/ml vs 149+/-10 ng/ml, ns) in patients with coronary atherosclerosis were not different from those in controls, as assessed by an analysis of covariance. After also adjusting for body mass index, hypertension, diabetes mellitus, and smoking by a multiple logistic function analysis, the association of sVCAM-1, sICAM-1, and sP-selectin with CHD was still not significant. Levels of sVCAM-1, sICAM-1, and sP-selectin were also not related to the extent of coronary atherosclerosis as judged by the number of stenosed vessels. However, inverse (p<0.05) relationships were observed between sVCAMs and serum levels of HDL3-cholesterol, apo A-II, and lipoprotein containing apo A-I and A-II, between sICAMs and levels of apo A-II and Lp A-I/A-II (Lp A-I/A-II), and between sP-selectin and lipoprotein containing only apo A-I. In conclusion, serum levels of soluble VCAM-1, ICAM-1, and P-selectin were not related to CHD or the extent of coronary atherosclerosis, but were inversely related to serum levels of high-density lipoprotein-related lipoproteins.
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PMID:Levels of soluble cell adhesion molecules in patients with angiographically defined coronary atherosclerosis. 1008 83

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