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)

Interaction between leukocyte and endothelial cells (ECs) is essential for vascular homeostasis and competent immune-inflammatory responses in vivo. Platelet-derived microparticles (PMPs) are generated by high shear stress and may appear in diseased small arteries and arterioles in various clinical settings. In this study, we used flow cytometry and confocal laser scanning microscopy to investigate the effects of high-shear-induced platelet and microparticle activation in adhesion molecules of THP-1 and ECs. We also measured the production of some cytokines and studied cytokine mRNA from THP-1 and ECs after PMP stimulation. PMP stimulation of THP-1 cells increased CD11b, CD32, and CD33 but not CD29, CD31, and CD36. PMP stimulation of ECs increased CD54 and CD63 but not CD9, CD29, and CD31. PMPs induced interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) production by THP-1. PMPs also induced IL-8, IL-1 beta, and interleukin-6 (IL-6) production by ECs. Production was time-dependent. With RT-PCR, some cytokine mRNAs were detected in THP-1 and ECs after PMP stimulation. In relation to adhesiveness after PMP stimulation, we could clearly observe a shift in distribution not only of CD11b in THP-1 cells but also of CD54 in ECs. In addition, anti-P-selectin glycoprotein ligand-1 antibody reduced the expression of CD11b, CD32, and CD33 in THP-1 after PMP stimulation. These results suggest that high-shear-induced microparticles may contribute to the development of atherosclerosis and participate in vascular damage in inflammatory disorders.
Atherosclerosis 2001 Oct
PMID:High-shear-stress-induced activation of platelets and microparticles enhances expression of cell adhesion molecules in THP-1 and endothelial cells. 1158 5

Monocyte-endothelial cell interactions have been implicated in the pathogenesis of a number of vascular diseases that target arterial and aortic endothelium, including atherosclerosis. Many different adhesion molecules, such as intercellular adhesion molecule (ICAM)-1, are thought to mediate monocyte binding to endothelial cells during the development of these diseases. However, conflicting results have been reported regarding the specific role of ICAM-1 in these events. In this study, we used a genetic approach to determine the contribution of ICAM-1 in mediating monocyte adhesion to mouse aortic endothelial cells (MAEC) derived from both wild-type and ICAM-1(-/-) mice. Treatment of wild-type MAEC with oxidized low-density lipoprotein significantly induced both WEHI 274.1 and whole blood monocyte adhesion, whereas similarly treated ICAM-1(-/-) MAEC showed a complete inhibition of monocyte binding. Dose-response treatment with tumor necrosis factor-alpha also increased monocyte adhesion to wild-type MAEC, but significant adhesion was only observed at higher doses for ICAM-1(-/-) MAEC. These data demonstrate a crucial role for ICAM-1-mediated monocyte-endothelial cell interactions in response to specific stimuli involved in inflammatory vascular diseases.
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PMID:Essential role of ICAM-1 in mediating monocyte adhesion to aortic endothelial cells. 1160 Apr 6

Laminar shear stress activates NADPH oxidase in vascular endothelial cells (ECs), and the generated superoxide radicals (O2(-.) are known to be involved in intercellular adhesion molecule (ICAM)-1 expression. In this study, the role of a glycosphingolipid (GSL), lactosylceramide (LacCer), as a second messenger in the shear-induced O2(-.) generation and ICAM-1 expression was examined. It is known that glucosylceramide synthase (GlcT-1) catalyzes the synthesis of glucosylceramide (GlcCer) from ceramide, and subsequently lactosylceramide synthase (GalT-2) synthesizes LacCer from GlcCer. We observed that exposing cultured human umbilical vein ECs (HUVECs) to fluid shear stress (20 dyn/cm(2) for 30 min) activated GalT-2. Shear stress also increased EC O2(-.) generation, that peaked at 30 min, and surface ICAM-1 protein expression at 6 h post-shear. EC preincubation with the antioxidant N-acetylcysteine (NAC; 20 mM for 2 h) completely abolished the shear-induced O2(-.) production and significantly inhibited ICAM-1 expression. EC preincubation with D-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), an inhibitor of the GSL glycosyltransferases GlcT-1 and GalT-2, abrogated the shear-induced activation of GalT-2. D-PDMP also abolished the shear-induced O2(-.) production and ICAM-1 expression. We conclude that laminar shear stress activates GalT-2 to produce LacCer. In turn, LacCer activates NADPH oxidase, which produces O2(-.), and O2(-.) mediates the shear-induced increase in ICAM-1 expression. Thus, LacCer may play an important role in hemodynamic force-induced pathological conditions, such as atherosclerosis and ischemia/reperfusion injury.
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PMID:Lactosylceramide mediates shear-induced endothelial superoxide production and intercellular adhesion molecule-1 expression. 1174 Jan 54

A critical event in the early stages of atherosclerosis is the focal accumulation of lipid-laden foam cells derived from macrophages. In various cholesterol-fed animal models of atherosclerosis, localized attachment of circulating monocytes to arterial endothelial cells appeared to precede the formation of foam cells. It is suggested that monocyte recruitment into early lesions depends on the endothelial adhesiveness for monocytes and lymphocytes. In vivo and in vitro experiments have identified molecules, such as ICAM-1, VCAM-1, and P-selectin, that can support the adhesion of monocytes and lymphocytes. Moreover, oxidized LDL, lysophosphatidyl-choline, and oxidized fatty acids induce the expression not only of these adhesion molecules but also of scavenger receptors, such as CD-36, SR-A, and LOX-1. Recently, we isolated and characterized the novel receptors for oxidized LDL, namely, LOX-1 and SR-PSOX. Expression of LOX-1 is found on endothelial cells, smooth muscle cells, and macrophages, whereas SR-PSOX is expressed on macrophages. In this paper the significance of oxidized LDL and its receptors, LOX-1 and SR-PSOX, in terms of atherogenesis is discussed.
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PMID:Role of oxidized LDL in atherosclerosis. 1179 67

Recent clinical evidence has indicated that the level of soluble ICAM-1 (sICAM-1) is correlated with the severity of atherosclerosis and can predict future cardiovascular events. Here, using apolipoprotein E (APOE)-deficient mice, we investigated the level of sICAM-1 in parallel with endothelial ICAM-1 expression and aortic atherosclerosis. We also examined the effect of ICAM-1 deficiency during the progression of atherosclerosis using double knockout mice. The level of sICAM-1 increased significantly in parallel with the progression of atherosclerosis in APOE-deficient mice, while the sICAM-1 level remained constant in wild-type mice from 3 to 10 months of age. ICAM-1 staining was detected in virtually all endothelial cells, however, ICAM-1 was expressed strongly in the endothelium overlying atheromatous palque in APOE-deficient mice. Deficiency of ICAM-1 in APOE-deficient mice significantly reduced lesions after 5 and 10 months. The present study supported the notion that the level of sICAM-1 is closely related with the severity of atherosclerosis and cardiovascular events, and also suggested that inhibition of ICAM-1 can delay the progression of atherosclerosis.
Atherosclerosis 2002 Feb
PMID:Involvement of ICAM-1 in the progression of atherosclerosis in APOE-knockout mice. 1184 52

The transcription factor, NFkB, plays a pivotal role in the coordinated transactivation of cytokine and adhesion molecule genes involved in atherosclerosis and lesion formation after vascular injury. We hypothesized that synthetic double-stranded DNA with high affinity for NFkB may be introduced as a 'decoy' cis element to bind the transcription factor, and block gene activation, resulting in an effective therapeutic agent for treating intimal hyperplasia. In vivo transfection of NFkB decoy oligodeoxynucleotides (ODN) into balloon-injured rat carotid artery resulted in the inhibition of neointimal formation at 14 days after injury as compared with vessels transfected with scrambled ODN (P < 0.01). It is of importance to note that in the vessels transfected with NFkB decoy ODN, the expression of p53, a pro-apoptotic gene, was upregulated in neointimal area, followed by increased apoptosis at 14 days. In addition, gene expression of ICAM-1 and VCAM-1 was markedly decreased in blood vessels transfected with NFkB decoy ODN compared with scrambled ODN, whereas balloon injury induced ICAM and VCAM expression in the neointimal area. More importantly, the migration of macrophages and T-lymphocytes into the neointima and media was significantly inhibited by NFkB decoy ODN as compared with scrambled ODN. Here, we demonstrated that in vivo transfer of NFkB decoy ODN successfully inhibited neointimal formation after balloon injury, accompanied by (1) induction of apoptosis through p53 upregulation, and (2) inhibition of local inflammatory actions through the downregulation of adhesion molecules. These results suggest that decoy treatment against NFkB provides a new therapeutic strategy to inhibit neointimal hyperplasia after angioplasty.
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PMID:Inhibition of intimal hyperplasia after balloon injury in rat carotid artery model using cis-element 'decoy' of nuclear factor-kappaB binding site as a novel molecular strategy. 1189 2

Migration and differentiation of monocytes to the intima of blood vessels may be a crucial first step in the development of atherosclerosis associated with Chlamydia (Chlamydophila) pneumoniae. However, the involvement of C. pneumoniae infection in such steps is not clear. In the present study, therefore, the differentiation-inducing activity of C. pneumoniae to monocytes was examined. Human THP-1 monocytic cell line cells were infected with C. pneumoniae, and the differentiation of monocytes to macrophages was assessed by cell morphology, phagocytic activity, and expression of a cell surface adhesion molecule. The monocytic cells infected with viable bacteria markedly differentiated into macrophages associated with diffused cell morphology, increased uptake of polystyrene beads and increased ICAM-1 (intercellular adhesion molecule 1) expression on the cell surfaces. Heat-killed bacteria did not induce any morphological changes or increase of phagocytosis, but they did induce an increase of cell surface ICAM-1 expressions in THP-1 monocytic cells. The antibiotic minocycline treatment of infected cells resulted in marked inhibition of the cell differentiation as well as C. pneumoniae growth in the cells, but not ICAM-1 expression. In addition, the experiments with human peripheral blood monocytes infected with C. pneumoniae also showed the differentiation of macrophages assessed by morphological change and phagocytic activity. These results indicate that C. pneumoniae infection may directly induce the differentiation of monocytes to macrophages. However, antigenic stimulation of monocytes with bacteria may not be sufficient for a full macrophage differentiation.
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PMID:Chlamydia pneumoniae infection induces differentiation of monocytes into macrophages. 1195 75

1. Obesity is known to increase the risk for atherosclerotic diseases. Serum levels of cellular adhesion molecules are reported to be indices of atherosclerosis. The aim of the present study was to assess the effect of weight reduction on soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin). 2. Eighteen non-diabetic normotensive obese women participated in a 3 month lifestyle-modification programme (intervention group). The programme consisted of lectures on diet, exercise sessions and behavioural modification by weight charting. Fourteen women who did not enter the programme served as controls. Body fat mass (FM) was measured by dual-energy X-ray absorptiometry. Soluble ICAM-1 and sE-selectin were measured by ELISA. 3. After 3 months, sICAM-1 and sE-selectin, as well as body FM, decreased in the intervention group (P < 0.001), while no changes were observed in the control group. The baseline sE-selectin was positively correlated with total body FM, trunk FM and percentage body fat (r = 0.50-0.57; P < 0.01), but not with leg FM. The change in sE-selectin was also correlated with changes in total body FM and trunk FM (both r = 0.46; P < 0.01). Baseline sICAM-1 was not significantly correlated with these variables. The associations between changes in sICAM-1 and changes in total body FM or trunk FM were of borderline significance (both r = 0.34; P = 0.06). Linear regression analysis indicated that the change in sE-selectin was explained by the change in trunk FM (R2 = 0.18; P < 0.01). 4. Soluble ICAM-1 and sE-selectin were positively correlated with obesity, especially with central obesity. Weight reduction resulted in decreases in soluble adhesion molecules, which may suggest a downregulation of endothelial activation.
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PMID:Weight reduction decreases soluble cellular adhesion molecules in obese women. 1201 Jan 83

One of the critical events in the early stage of atherosclerosis is the focal accumulation of lipid-laden foam cells derived from macrophages. In various cholesterol-fed animal models of atherosclerosis, it was found that localized attachment of circulating monocytes to arterial endothelial cells appears to precede the formation of foam cells. It has been suggested that monocyte recruitment into early lesions is depend upon the endothelial adhesiveness for monocytes and lymphocytes. In vivo and in vitro experiments have identified molecules, such as ICAM-1, VCAM-1 and P-selecin, those can support the adhesion of monocytes and lymphocytes. Moreover oxidized LDL, lysophosphatidylcholine and oxidized fatty acids induce the expression of not only these adhesion molecules but also scavenger receptors, such as CD-36, SR-A and LOX-1. Recently we isolated and characterized the novel receptors for oxidized LDL, named LOX-1 and SR-PSOX. The expression of LOX-1 is found on endothelial cells, smooth muscle cells and macrophages. Whereas SR-PSOX expresses on macrophages. We address in this paper on the significance of hyperlipidemia, especially oxidized LDL and its receptors in terms of atherosclerosis.
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PMID:[Hyperlipidemia and atherosclerosis]. 1202 85

Atherosclerosis underlies late occlusion of human saphenous vein (HSV) coronary artery bypass grafts. Monocyte infiltration is implicated, but its mechanisms are unclear given that HSV normally expresses the ICAM-1 but not the VCAM-1 adhesion molecule. To define the mechanisms underlying monocyte adhesion, samples of HSV taken from coronary artery bypass graft patients were co-cultured with human monocytes and adherent monocytes were quantified by immunocytochemistry for CD68 on transverse sections. Pre-treatment of veins with anti-ICAM-1 antibodies reduced monocyte adhesion (monocytes/mm of section) from 7.2 +/- 1.5 to 3.1 +/- 0.7 (p < 0.05, n = 6), but the effect of anti-VCAM-1 was not significant (4.1 +/- 0.7). Paradoxically, pre-treatment of monocytes with either anti-beta(2)-integrins, the counter-receptor of ICAM-1, or anti-alpha(4) integrins, the counter-receptor of VCAM-1, significantly reduced adhesion (1.8 +/- 0.6 and 2.4 +/- 0.7, respectively, p < 0.05). These results were clarified by immunocytochemistry, which confirmed that VCAM-1 expression was absent in harvested vein but was induced in the endothelium during co-culture. Consistent with this, when anti-ICAM-1 or anti-VCAM-1 was present throughout co-culture, either of them reduced adhesion (from 4.2 +/- 0.9 to 2.3 +/- 0.5 and 2.2 +/- 0.4, respectively, p < 0.02, n = 8) and there was no further effect of adding both (2.0 +/- 0.5). These results demonstrate that both ICAM-1/beta(2) and VCAM-1/alpha(4) integrin interactions mediate monocyte adhesion to HSV, possibly as part of a common pathway. These experiments imply that either integrin might be targeted to reduce monocyte infiltration into HSV grafts.
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PMID:Both ICAM-1- and VCAM-1-integrin interactions are important in mediating monocyte adhesion to human saphenous vein. 1209 20

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