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

Low and oscillatory shear stresses are major features of the hemodynamic environment of sites opposite arterial flow dividers that are predisposed to atherosclerosis. Atherosclerosis is a focal inflammatory disease characterized initially by the recruitment of mononuclear cells into the arterial wall. The specific characteristics of the hemodynamic environment that facilitate the generation of arterial inflammatory responses in the presence of, for example, hyperlipidemia are unknown. We show here that prolonged oscillatory shear stress induces expression of endothelial cell leukocyte adhesion molecules, which are centrally important in mediating leukocyte localization into the arterial wall. Vascular cell adhesion molecule-1 was upregulated an average 9-fold relative to endothelial monolayers in static culture. Intercellular adhesion molecule-1 and E-selectin exhibited 11-fold and 7.5-fold increases, respectively. Upregulation of these adhesion molecules was associated with enhanced monocyte adherence. Cytokine stimulation of surface vascular cell adhesion molecule-1 was maximally induced after 6 and 8 hours of cytokine incubation. Oscillatory shear stress for these time periods elicited respective vascular cell adhesion molecule-1 levels of 16% and 30% relative to those observed for cytokine stimulation. Surface intercellular adhesion molecule-1 induction by cytokine stimulation for 24 hours was found to be approximately five times the level detected after 24 hours of oscillatory shear stress. Experiments performed in the presence of the antioxidant N-acetylcysteine demonstrated that the expression of vascular cell adhesion molecule-1 could be almost totally abolished, whereas that of intercellular adhesion molecule-1 was typically reduced by approximately 70%. These results imply that oscillatory shear stress per se is sufficient to stimulate mononuclear leukocyte adhesion and, presumptively, migration into the arterial wall. These results further indicate that atherosclerotic lesion initiation is likely related, at least in part, to unique signals generated by oscillatory shear stress and that the mechanism of upregulation is, to some extent, redox sensitive.
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PMID:Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. 952 57

Treatment of human umbilical vein endothelial cells (HUVEC) with oxidized low density lipoprotein (ox-LDL, 100 microg/ml) for 24 h increased adhesion of human monocytic Mono Mac 6 cells from 4.8 +/- 0.9% to 17.6 +/- 2.5% (P < 0.001). The effect was dose dependent and first evident at 10 microg/ml ox-LDL. In contrast, adhesion of U937 cells was not significantly increased. Mac-1 (CD11b/CD18), a monocytic counter-receptor for intercellular adhesion molecule-1 (ICAM-1), that also binds to heparin, is present on Mono Mac 6 but not on U937 cells, and may thus explain these differences in adhesion. Consistently, ox-LDL induced a 2-fold upregulation of ICAM-1 surface expression on HUVEC. The presence of maltose-1-phosphate or heparin but not monoclonal antibodies (mAbs) to ICAM-1 reduced adhesion of Mono Mac 6 cells to untreated HUVEC. Combinations of mAbs to ICAM-1 with either maltose-1-phosphate or heparin inhibited Mono Mac 6 adhesion to ox-LDL-stimulated HUVEC by more than 50%, while either alone had no effect. This suggests that two distinct endothelial ligands for Mac-1, inducible ICAM-1 and carbohydrate-decorated heparin-like proteoglycan structures mediate monocytic cell interaction with ox-LDL-treated HUVEC. The stimulating activity in ox-LDL could partly be transfered to bovine serum albumin, while lysophosphatidylcholine or 8-epi prostaglandin F2alpha produced no stimulatory effects. The inhibition of ox-LDL effects with the antioxidant PDTC indicates radicals as possible mediators. In conclusion, we show that oxidatively modified LDL induces adhesion of monocytic cells, which utilize at least two distinct adhesive receptors on endothelium, one being identified as ICAM-1.
Atherosclerosis 1998 Feb
PMID:Monocytic cell adhesion to endothelial cells stimulated by oxidized low density lipoprotein is mediated by distinct endothelial ligands. 954 1

We investigated the effects of risk factors of atherosclerosis on soluble intercellular adhesion molecule-1 (sICAM-1) concentration and leukocyte count by using multivariate statistical analysis. The subjects were 90 people who were hospitalized for a complete check-up examination. Eight risk factors were selected as candidates for predictor variables: age, body mass index (BMI), uric acid, glycohemoglobin A1c, number of cigarettes smoked daily, total cholesterol, triglyceride, and high density lipoprotein (HDL)-cholesterol. The predictor variables were selected using a stepwise method, [criterion variable - predictor variable (standardized regression coefficient)]; sICAM1 - age (0.1859), number of cigarettes (0.2558), triglyceride (0.2447); leukocytes - number of cigarettes (0.2827), triglyceride (0.2526), HDL-cholesterol (-0.2800); stab leukocytes - number of cigarettes (0.2460); segmented leukocytes - glycohemoglobin A1c (0.1495), number of cigarettes (0.2716), HDL-cholesterol (-0.3254); lymphocytes - BMI (0.2639), number of cigarettes (0.1495), triglyceride (0.3520); monocytes - glycohemoglobin A1c (0.2617). These findings indicated that the risk factors of atherosclerosis may influence sICAM1 concentration and leukocyte count.
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PMID:Relationship among risk factors of atherosclerosis, leukocyte count, and soluble intercellular adhesion molecule-1. 955 May 90

A unique peripheral vascular disorder called 'blackfoot disease' is endemic in a limited area on the south-west coast of Taiwan. Clinically, the signs and symptoms of blackfoot disease (BFD) are similar to those of arteriosclerosis and Buerger's disease. A destruction of vascular endothelial cells (ECs) takes place at an early stage in the affected limbs. Currently, the cause of BFD is believed to be artesian drinking water containing a high concentration of arsenic and/or humic substances, although the mechanism of EC destruction is not entirely understood. The purpose of the present study was to examine the factors related to EC damage in BFD. Thus, we investigated the effects of purified IgG collected from patients with BFD (BFD-IgG) and from normal controls (N-IgG) on cultured EC. We found that: (1) EC binding activity of BFD-IgG was significantly higher than that of N-IgG; (2) BFD-IgG, at a concentration higher than 100 microg/ml but not N-IgG, induced concentration-dependent EC cytotoxicity; (3) BFD-IgG at a concentration of 100 microg/ml stimulated neither the release of von Willebrand factor nor the expression of intercellular adhesion molecule-1 by EC. Fluorescent video microscopic examination revealed an increase in transcapillary and interstitial diffusion of nailfold capillary loops in clinically normal fingers of BFD patients. These findings strongly suggested that immunological mechanisms played a significant role in the pathogenesis of BFD. We propose that only persons who produce the IgG anti-endothelial cell antibody are potential victims of BFD.
Atherosclerosis 1998 Mar
PMID:In vitro cytotoxicity of IgG antibodies on vascular endothelial cells from patients with endemic peripheral vascular disease in Taiwan. 956 46

In health, the vascular endothelium forms a multifunctional interface between the circulating blood and various tissues and organs of the body. It constitutes a selectively permeable barrier for macromolecules, as well as a nonthrombogenic and nonadhesive container that actively maintains the fluidity of blood. It is a metabolically active endocrine organ, serving as the source of multiple factors and mediators that are critical for normal homeostasis. These include vasodilators (nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor), vasoconstrictors (endothelin-1, thromboxane A2, prostaglandin H2 and components of the renin angiotensin system), various pro- and antithrombotic factors (e.g. tissue factor, platelet activating factor--PAF, von Willebrand factor), fibrinolytic activators and inhibitors (e.g. tissue plasminogen activator, plasminogen activator inhibitor-1), potent arachidonate metabolites (prostanoids), leukocyte adhesion molecules (e.g. E-selectin, P-selectin, intercellular adhesion molecule-1--ICAM-1, vascular cell adhesion molecule-1--VCAM-1), and multiple cytokines with activities of growth stimulators and inhibitors, transforming growth factors, proinflammatory and antiinflammatory mediators, tumour necrosis factors and chemotactic factors (chemokines). Besides these essential activities controlling the cardiovascular system, the endothelial cells represent an important part of the immune system as well. They have a pivotal role in the initiation and development of defensive and damaging inflammatory responses. Therefore endothelium can be considered as being the central equipment for the mutual exchange of life important information between the cardiovascular and immune systems. This in turn is leading to rapid advances in understanding the pathogenesis of some of the most serious and most common diseases, including inflammation, atherosclerosis and hypertension. (Tab. 7, Ref. 89.)
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PMID:[Vascular endothelium as a factor in information transfer between the cardiovascular and immune systems]. 958 73

Hypertriglyceridemia may contribute to the development of atherosclerosis by increasing expression of cell adhesion molecules (CAMs). Although the cellular expression of CAMs is difficult to assess clinically, soluble forms of CAMs (sCAMs) are present in the circulation and may serve as markers for CAMs. In this study, we examined the association between sCAMs and other risk factors occurring with hypertriglyceridemia, the effect of triglyceride reduction on sCAM levels, and the role of soluble vascular cell adhesion molecule-1 (sVCAM-1) in monocyte adhesion in vitro. Compared with normal control subjects (n=20), patients with hypertriglyceridemia and low HDL (n=39) had significantly increased levels of soluble intercellular adhesion molecule-1 (sICAM-1) (316+/-28.8 versus 225+/-16.6 ng/mL), sVCAM-1 (743+/-52.2 versus 522+/-43.6 ng/mL), and soluble E-selectin (83+/-5.9 versus 49+/-3.6 ng/mL). ANCOVA showed that the higher sCAM levels in patients occurred independently of diabetes mellitus and other risk factors. In 27 patients who received purified n-3 fatty acid (Omacor) 4 g/d for > or =7 months, triglyceride level was reduced by 47+/-4.6%, sICAM-1 level was reduced by 9+/-3.4% (P=.02), and soluble E-selectin level was reduced by 16+/-3.2% (P<.0001), with the greatest reduction in diabetic patients. These results support previous in vitro data showing that disorders in triglyceride and HDL metabolism influence CAM expression and treatment with fish oils may alter vascular cell activation. In a parallel-plate flow chamber, recombinant sVCAM-1 at the concentration seen in patients significantly inhibited adhesion of monocytes to interleukin-1-stimulated cultured endothelial cells under conditions of flow by 27.5+/-7.2%. Thus, elevated sCAMs may negatively regulate monocyte adhesion.
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PMID:Soluble cell adhesion molecules in hypertriglyceridemia and potential significance on monocyte adhesion. 959 30

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

We examined the relationship of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) with smoking and hypercholesterolaemia in peripheral artery disease (PAD). Serum samples were obtained from 119 patients with objectively-proven PAD, 39 patients with hypercholesterolaemia but asymptomatic for PAD, and 132 age and sex matched asymptomatic controls. Using ELISAs, we found increased sICAM-1 and sVCAM-1 (both p <0.01) in the patients with PAD relative to the controls, but no significant change in patients with hypercholesterolaemia. However, the effect for sVCAM-1 was lost when smoking was entered as a covariate. Only sICAM-1 was higher in patients with PAD in the femoral/iliac arteries compared to the carotid arteries (p <0.05). In a 39-month follow-up of 112 patients with PAD, increased ICAM-1 weakly (univariate p <0.05) predicted those 57 whose disease progressed (i.e. to end points such as myocardial infarction and arterial surgery). However, high fibrinogen was a much better (univariate p = 0.001, multivariate p <0.05) predictor of disease progression. We suggest (i) that increased levels of sVCAM-1 in atherosclerosis are due to smoking, (ii) that increased sICAM-1 is independent of this risk factor, (iii) that both these changes are independent of hypercholesterolaemia, and (iv) that increased sICAM-1 is a weak predictor of disease progression in peripheral atherosclerosis.
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PMID:Circulating ICAM-1 and VCAM-1 in peripheral artery disease and hypercholesterolaemia: relationship to the location of atherosclerotic disease, smoking, and in the prediction of adverse events. 965 27

Atherosclerosis is known to be accelerated in patients with diabetes mellitus. We have examined the effect of glucose on the expression of intercellular adhesion molecule-1 (ICAM-1) in cultured human umbilical vein endothelial cells (HUVEC) and the adhesion of cells of monocyte-like cell line, THP-1, to HUVEC. HUVEC exposed to a high glucose concentration (16.7 mM) showed a 1.4-fold increase in the adhesion of THP-1 cells and a 1.3-fold increase in cell surface expression of ICAM-1 after 6 h exposure compared with those cultured in medium with a low glucose concentration (5.6 mM). ICAM-1 expression began to increase after 3 h exposure, was maximal at 6 h and gradually decreased afterwards. At 16.7 mM, raffinose stimulation produced a significantly lower expression of ICAM-1 on HUVEC than glucose, furthermore it caused a significantly lower expression than low glucose stimulation (5.6 mM). We conclude that a high concentration of glucose can induce ICAM-1 in endothelial cells and that this effect may play an important role in atherogenesis in patients with diabetes mellitus.
Atherosclerosis 1998 May
PMID:High concentration of glucose induces the expression of intercellular adhesion molecule-1 in human umbilical vein endothelial cells. 967 69

Atherosclerotic plaques develop in the arterial wall from complex multicellular processes following the early recruitment of circulating monocytes. Infiltration of monocytes is mediated by cell adhesion molecules (CAMs), including vascular cell adhesion molecule-1 (VCAM-1) which is rapidly induced in endothelial cells in response to cytokines. Apolipoprotein E (apo E), a 34-kDa polypeptide, helps protect against atherosclerosis, in part, because apo E phospholipid particles secreted by macrophages may have local protective effects within lesions. Here we have investigated whether purified plasma apo E, complexed with dimyristoyl phosphatidylcholine (DMPC) vesicles, can inhibit cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human umbilical vein endothelial cells (HUVECs). Expression of VCAM-1 in endothelial cells after exposure to tumour necrosis factor-alpha (TNF-alpha) or interleukin 1beta (IL-1beta) was quantified by ELISA and shown to be partially inhibited by 17beta-estradiol (40-60% inhibition) or by S-nitroso-L-glutathione, a nitric oxide donor (20-25%). However, preincubations with physiological concentrations (10-100 microg protein/ml) of apo E DMPC did not downregulate VCAM-1 expression, even with extended preincubation times. These findings were confirmed using a fluorescence-activated cell sorter (FACS) for analysis which indicated additionally that apo E-DMPC had no effect on sub-populations within the HUVEC cultures. Finally, apo E-DMPC vesicles were also unable to suppress TNF-alpha-induced upregulation of E-selectin or intercellular adhesion molecule-1 (ICAM-1). We conclude that plasma apo E is unlikely to be important in limiting endothelial activation.
Atherosclerosis 1998 Jul
PMID:Apolipoprotein E and regulation of cytokine-induced cell adhesion molecule expression in endothelial cells. 969 92


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