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

The participation of leukocytes in the development of vascular disorders has been observed under various circumstances. Leukocyte activation occurs in extracorporeal blood circulation which lead to a pulmonary vascular sequestration and respiratory distress syndrome. Leukocytes could act on vascular components through at least two different pathways by releasing free oxygen radicals and proteases or by producing mediators such as interleukin 1, Tumor necrosis alpha, leukotrienes. Monocytes macrophages are present in the vascular wall at a very early stage of atherosclerosis. A majority of foam cells have been identified as macrophages loaded with lipids. Lymphocytes and monocytes are present in the atherosclerotic plaque. Leukocytes are also observed in the inflammatory lesion of vasculitis and experimentally activated lymphocytes can induce vasculitis. The molecular bases of leukocyte-endothelium interactions have been determined, and imply specialized molecules. Leukocyte Adhesion Molecule (LeucAM) appear to play a crucial role in leukocyte adhesion. On the endothelial cell side, endothelial cell adhesion molecule, intercellular adhesion molecule are receptors for leukocytes adhesion. They have been recently fully characterized. The better knowledge of leukocyte-vascular wall interactions offers new possible target for therapeutic agents.
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PMID:[Leukocytes and vascular lesions]. 204 28

While an elevated plasma concentration of HDLs is protective against the development of atherosclerosis and ensuing coronary heart disease (CHD), the mechanism of this protection is unknown. One early cellular event in atherogenesis is the adhesion of mononuclear leukocytes to the endothelium. This event is mediated principally by vascular cell adhesion molecule-1 (VCAM-1) but also involves other molecules, such as intercellular adhesion molecule-1 (ICAM-1) and E-selectin. We have investigated the effect of isolated plasma HDLs and reconstituted HDLs on the expression of these molecules by endothelial cells. We show that physiological concentrations of HDLs inhibit tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 (IL-1) induction of these leukocyte adhesion molecules in a concentration-dependent manner. Steady state mRNA levels of TNF-alpha-induced VCAM-1 and E-selectin are significantly reduced by physiological concentrations of HDLs. An an HDL concentration of 1 mg/mL apolipoprotein A-I, the protein expressions of VCAM-1, ICAM-1, and E-selectin were inhibited by 89.6 +/- 0.4% (mean +/-SD, n=4), 64.8 +/- 1.0%, and 79.2 +/- 0.4%, respectively. In contrast, HDLs have no effect on the expression of platelet endothelial cell adhesion molecule (PECAM) or on the expression of the p55 and p75 subunits of the TNF-alpha receptor. HDLs were effective when added from 16 hours before to 5 minutes after cytokine stimulation. HDLs had no effect on TNF-alpha-induced expression of ICAM-1 by human foreskin fibroblasts, suggesting that the effect is cell-type restricted.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules. 758 80

The adherence of circulating monocytes to the endothelium, their migration into the subendothelium, and the subsequent formation of foam cells are initial events in the pathogenesis of atherosclerosis. However, the effect of hyperglycemia on the transendothelial migration of monocytes is not known. Exposure of human umbilical vein endothelial cells (HUVEC) cultured in a Transwell chamber to 25 mM D-glucose (a concentration representing a hyperglycemic state) for 2 h resulted in a twofold increase in the migration of vitamin D3-differentiated monocyte-like HL-60 cells. The migration was inhibited by addition of either an antibody to platelet-endothelial cell adhesion molecule-1 (PECAM-1) or a protein kinase C inhibitor, GF-109203X. In HUVEC, high concentrations of D-glucose (25 mM), but not of other sugars such as L-glucose, 2-deoxyglucose, D-galactose, or D-mannitol, caused a sevenfold increase in the phosphorylation of PECAM-1 as a result of activation of protein kinase C. The 25 mM D-glucose-induced PECAM-1 phosphorylation and transmigration of monocyte-like HL-60 cells were further increased by treatment of HUVEC with the phosphatase inhibitor calyculin A. These results suggest that direct phosphorylation of PECAM-1 in response to elevated glucose promotes transendothelial migration of monocytes, contributing to accelerated atherogenesis in diabetics.
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PMID:Glucose-induced transmigration of monocytes is linked to phosphorylation of PECAM-1 in cultured endothelial cells. 889 59

Focal recruitment of monocytes and lymphocytes is one of the earliest detectable cellular responses in the formation of lesions of atherosclerosis. This localized accumulation of leukocytes is a multistep process in which the endothelium remains intact and may regulate leukocyte recruitment by expressing specific adhesion molecules. To examine the relationship of adhesion molecule expression to initiation factors and the sites of lesion formation, we analyzed the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and platelet-endothelial cell adhesion molecule-1 (PECAM-1) en face on the aortic endothelium of control mice and homozygous apolipoprotein E-deficient (ApoE -/-) mice that develop complex lesions of atherosclerosis similar to those in humans. In control mice, VCAM-1 staining was weak and limited to sites of altered blood flow. In contrast, in the ApoE -/- mice, VCAM-1 appeared to be localized over the surface of groups of endothelial cells in lesion-prone sites. Expression of VCAM-1 preceded lesion formation, and increased expression above control levels appeared to be correlated with the extent of exposure to plasma cholesterol. Although ICAM-1 was the most prominent adhesion molecule in lesion-prone sites, its expression appeared to be independent of plasma cholesterol levels and was upregulated in both ApoE -/- and control mice. At lesion-prone sites associated with altered blood flow, ICAM-1 was located over the surface of each endothelial cell and on microvilli, whereas VCAM-1 was confined to the cell periphery in non-lesion-prone sites. PECAM-1 was localized at the cell periphery throughout the aorta, and its expression did not appear to be regulated. Thus, the levels, localization, and characteristics of expression of VCAM-1, ICAM-1, and PECAM-1 appear to be differentially regulated. Upregulation of VCAM-1 and ICAM-1 is associated with sites of lesion formation.
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PMID:Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse. 959 45

The objective of this study was to determine whether the microvascular responses to ischemia and reperfusion (I/R) are altered in an animal model of atherosclerosis, the low-density lipoprotein-receptor knockout (LDLr -/-) mouse. Intravital video microscopy was used to monitor venular wall shear rate, leukocytes rolling velocity, the number of rolling, adherent and emigrated leukocytes, and albumin leakage in cremasteric postcapillary venules of wild-type (B6129) and LDLr -/- mice exposed to 60 min of ischemia and 60 min of reperfusion. The postcapillary venules of LDLr -/- mice exhibited two- to threefold larger increments in the number of adherent leukocytes and a more profound albumin leakage response to I/R than venules in wild-type mice. The exaggerated inflammatory responses noted in LDLr -/- mice placed on a normal diet were not exacerbated by a high-cholesterol diet. Treatment of LDLr -/- mice with either a platelet-activating factor (PAF) receptor antagonist (WEB-2086) or a monoclonal antibody (YN-1) against the endothelial cell adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), markedly attenuated the I/R-induced leukocyte adherence and albumin leakage. These findings indicate that atherogenic mice are more vulnerable to the deleterious microvascular effects of I/R and that PAF-mediated, ICAM-1-dependent leukocyte adhesion contributes to this exaggerated response to I/R.
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PMID:Ischemia-reperfusion induced microvascular responses in LDL-receptor -/- mice. 1033 Feb 50

Atherosclerosis causes occlusions in as many as 50% of human saphenous vein coronary artery bypass grafts. Monocyte infiltration is an early step in saphenous vein-graft atherosclerosis, however, comparatively little is known of its underlying mechanisms. As a first approach, we sought to define the occurrence, location and regulation of leukocyte adhesion molecules in human saphenous vein before and after surgical preparation for grafting, during neointima formation in culture and on stimulation with inflammatory cytokines. We compared the distribution of intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1) and platelet endothelial cell adhesion molecule (PECAM-1 or CD-31) in endothelial cells and smooth muscle cells (SMCs), using immunocytochemistry. ICAM-1 was expressed on endothelial cells before culture and on both endothelial cells and medial or neointimal SMCs after culturing vein for 14 days in 30% foetal bovine serum or after culturing for 24 h with TNF-alpha. Relative tissue levels of ICAM-1 measured by Western blotting were significantly elevated by culturing freshly-isolated (0.02+/-0.01 to 0.18+/-0.03) and surgically-prepared (0.02+/-0.01 to 0.14+/-0.03; n=6) veins or following TNF-alpha treatment of surgically-prepared veins (0.04+/-0.01 to 0.32+/-0.11, n=7). VCAM-1 was undetectable before or after culturing but was strongly upregulated on endothelial cells by incubation with the cytokines TNF-alpha, IL-1alpha or interferon-gamma. PECAM-1 was expressed constitutively on endothelial cells. We conclude that human saphenous vein expresses several adhesion molecules capable of mediating monocyte migration. The increased expression of ICAM-1 in SMC after culturing or cytokine treatment and of VCAM-1 in endothelial cells suggests that interactions with beta1 and beta2 integrins are important pathways for stimulated monocyte ingress into human saphenous vein grafts.
Atherosclerosis 2000 May
PMID:Expression of intercellular adhesion molecules in human saphenous veins: effects of inflammatory cytokines and neointima formation in culture. 1078 33

While there is a growing body of evidence suggesting that hypercholesterolemia prior to the onset of atherosclerosis renders tissues more susceptible to inflammation, the mechanisms that underlie this exaggerated inflammatory response remain poorly defined. The overall objective of this study was to assess the influence of hypercholesterolemia on endotoxin-induced endothelial cell adhesion molecule (CAM) expression in different vascular beds. Another objective was to determine whether the altered endothelial CAM expression in hypercholesterolemic animals is associated with a corresponding change in plasma cytokine levels. Male Sprague/Dawley rats (SD) were placed either on a normal (control) or high cholesterol (HC) diet for 3 weeks. The dual radiolabeled monoclonal antibody (mAb) technique was used to measure the expression of P-selectin, E-selectin, ICAM-1, and VCAM-1 in different vascular beds after intraperitoneal injection of endotoxin (LPS) derived from Salmonella abortus equi. LPS induced a significant increase in the expression of all endothelial CAMs in both normocholesterolemic and hypercholesterolemic groups. However, hypercholesterolemia enhanced LPS-induced expression of P-selectin, E-selectin, and ICAM-1 in several vascular beds, while VCAM-1 expression was unaffected. Thrombocytopenia, induced with anti-platelet serum, did not alter LPS-induced P-selectin expression in either group, suggesting that platelets do not contribute to this response. Hypercholesterolemia was associated with an exaggerated increase in plasma TNF-alpha, but not IL-1beta, after LPS treatment. These results indicate that hypercholesterolemia in rats may render tissues more vulnerable to the inflammatory effects of LPS by enhancing the expression of certain endothelial CAMs.
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PMID:Hypercholesterolemia alters endotoxin-induced endothelial cell adhesion molecule expression. 1144 15

Inflammation and genetics are both prominent mechanisms in the pathogenesis of atherosclerosis and arterial thrombosis. Accordingly, a number of population studies have explored the association of ischaemic heart disease with gene polymorphisms of the inflammatory molecules tumour necrosis factors (TNF) alpha and beta, transforming growth factors (TGF) beta1 and 2, interleukin (IL) 1 and its receptor antagonist (IL 1ra), CD14 (the receptor for lipopolysaccharide), P and E selectins, and platelet endothelial cell adhesion molecule (PECAM) 1. Although they are very preliminary and partly conflicting, the data provide some evidence that alterations in the genetics of the inflammatory system may modify the risk of ischaemic heart disease.
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PMID:Inflammatory gene polymorphisms and ischaemic heart disease: review of population association studies. 1179 41

There are several potential mechanisms by which HDLs protect against atherosclerosis. One relates to the ability of HDLs to promote the efflux of cholesterol from macrophages. Another is the ability of HDLs to inhibit one of the earliest events in the development of atherosclerosis, namely the expression of vascular cell adhesion molecules in activated endothelial cells. This property has been reported in vitro in studies with both native and reconstituted HDLs. The inhibitory activity of reconstituted HDLs is influenced by the phospholipid composition of the particles. An inhibition of endothelial cell adhesion molecule expression has also been observed in some (but not all) studies conducted in vivo in mice and pigs. The mechanism of this potentially anti-atherogenic effect of HDLs remains uncertain, as does its contribution to the cardioprotective effects of HDLs in vivo.
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PMID:Effect of high-density lipoproteins on the expression of adhesion molecules in endothelial cells. 1204 98

E-selectin is a cytokine-inducible endothelial cell adhesion molecule that binds a restricted population of T lymphocytes consisting of Th1 memory cells bearing the cutaneous lymphocyte Ag (CLA). A serine to arginine (S128R) polymorphism in E-selectin has been reported at increased frequency in patients with systemic lupus erythematosus and atherosclerosis. Here we tested the hypothesis that the S128R substitution may contribute to increased vascular disease by altering the number and/or phenotype of lymphocytes interacting with E-selectin under shear flow. We observed that CHO cell monolayers transfected with S128R recruited significantly greater numbers of unfractionated lymphocytes than monolayers expressing an equivalent density of wild-type (WT) E-selectin. Depletion of the CLA(+) subpopulation or generation of CLA(-) lymphoblasts abolished rolling and arrest on WT E-selectin, but left a residual population that interacted with S128R. Generation of Th subsets revealed preferential interaction of Th0 and Th2, but not Th1, cells with S128R compared with WT. However, only T cells of a memory phenotype interacted with S128R, since neither monolayer supported rolling of CD45RA(+) cells. Our results demonstrate that the S128R polymorphism extends the range of lymphocytes recruited by E-selectin, which may provide a mechanistic link between this polymorphism and vascular inflammatory disease.
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PMID:Enhanced recruitment of Th2 and CLA-negative lymphocytes by the S128R polymorphism of E-selectin. 1242 68


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