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)

Several studies during recent years have demonstrated the potential for vascular smooth muscle cells (SMC) and dermal fibroblasts to participate in immune interactions such as antigen presentation and alloreactivity. The molecular interactions mediating lymphocyte adhesion to these mesenchymal cells have, however, not previously been characterized in detail. In the present study we demonstrate ICAM-1 (CD54) expression by cultured human SMC and its up-regulation by IL-1, IFN-gamma, and bacterial lipopolysaccharide. Monoclonal antibodies were used to define the molecular interactions in the adhesion of 51Cr-labelled T lymphoblasts to adherent SMC and fibroblasts. ICAM-1 appeared to mediate adhesion of T lymphocytes by binding to the beta 2-integrin CD11a/CD18 (LFA-1) expressed by the lymphoblasts. We present evidence for the involvement of at least three different mechanisms in the adhesion of activated T lymphocytes to cultured fibroblasts. It was found that beta 2-integrin-mediated interaction could only account for less than half of the binding activity. The remaining adhesion was partly mediated by beta 1-integrins, presumably via VLA-5 since an anti-VLA-5 antibody and an RGD-containing peptide blocked adhesion to the same degree. However, antibodies to beta 1-, beta 2-, and beta 3-integrin subunits added together only inhibited adhesion by approximately 50%. The residual adhesion could be blocked by inhibition of cell metabolism and was increased by stimulation of the lymphocytes with phorbol ester, suggesting involvement of other, as yet undefined, adhesion molecules. The molecular interactions between lymphocytes and mesenchymal cells demonstrated in this study may have implications in several inflammatory conditions such as vasculitis, atherosclerosis, and connective tissue diseases.
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PMID:Adhesion of activated T lymphocytes to vascular smooth muscle cells and dermal fibroblasts is mediated by beta 1- and beta 2-integrins. 138 Jan 79

An experimental system is described in which coronary arteries of mouse hearts transplanted heterotopically develop obstructive lesions by 4 weeks. Transient immunosuppression permits graft survival. Donor/recipient antigenic differences may be either class I or class II major histocompatibility antigens (H-2) or non-H-2 antigens. An infiltrate including CD4+ and CD8+ T lymphocytes and macrophages concentrates early in the intima and adventitia of larger coronary arteries, with little in the myocardium. Subsequently, the intima expands with cells of donor origin and the infiltrate invades the media. Endothelial and intimal cells express ICAM-1, leukocytes LFA-1: Endothelium expresses class I, but not class II, antigens. As class II disparity alone suffices, the endothelium can apparently be an indirect target of immune injury. We propose that graft atherosclerosis is T cell initiated and elicited by heterogeneous antigens in the endothelium or media. It is separable from rejection of the myocardium.
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PMID:Coronary atherosclerosis in transplanted mouse hearts. I. Time course and immunogenetic and immunopathological considerations. 790 94

Bacterial cell-wall lipopolysaccharide (LPS) is the main endotoxin contributing to local inflammation and systemic toxicity during Gram-negative infections and induces aortic endothelial injury with or without cell death and replication followed by increased leukocyte adhesion. Heat-shock protein (hsp) 60 is under study in our laboratory as a potential antigen inducing immunologic attack to endothelial cells in atherogenesis. To investigate the mechanism of LPS-induced endothelial injury and the phenotypes of adhering cells, Lewis rats were treated in vivo or, in aortic organ cultures, with LPS to determine the expression of intercellular-adhesion molecule-1 (ICAM-1) and hsp60 on aortic endothelium and to characterize phenotypes of adhering leukocytes. Increased ICAM-1 expression by aortic endothelium was observed as early as 3 hr after LPS injection and persisted up to 72 hr, whereas elevated levels of hsp60 were found between 6 and 48 hr. In vitro application of various types of stress, such as LPS, H2O2, and high temperature, not only stimulated endothelial expression of hsp60 but, concomitantly, that of ICAM-1. The number of adhering leukocytes was significantly increased on aortic endothelium 6 hr after LPS administration, and the predominant leukocytes adhering to stressed endothelium were monocytes (80%) and T lymphocytes (8 to 20%). In organ cultures of rat aortic intimal, LPS, and H2O2 evoked increased leukocyte adhesion, which proved to be selective, because adherent leukocytes were mostly Ia+ monocytes and T cells, i.e., activated. Adhering T cells were gamma/delta antigen-receptor positive in 8 to 16% after LPS stress, whereas these cells amount to only 2 to 4% of peripheral blood T cells. Blocking of adhesion molecules ICAM-1, LFA-1 alpha, and/or LFA-1 beta reduced adhesion up to 34%. Increased coordinated LPS-dependent expression of hsp60 and ICAM-1 correlates with monocyte and T-cell adhesion to aortic endothelium. These observations may be significant for elucidating the mechanism of the initiating events in the development of atherosclerosis.
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PMID:Coexpression of heat-shock protein 60 and intercellular-adhesion molecule-1 is related to increased adhesion of monocytes and T cells to aortic endothelium of rats in response to endotoxin. 856 88

The intercellular adhesion molecule (ICAM) 1 is an Ig-like cell adhesion molecule expressed by several cell types, including leukocytes and endothelial cells. It can be induced in a cell-specific manner by several cytokines, for example, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma, and inhibited by glucocorticoids. Its ligands are the membrane-bound integrin receptors LFA-1 and Mac-1 on leukocytes, CD43, the soluble molecule fibrinogen, the matrix factor hyaluronan, rhinoviruses, and Plasmodium falciparum malaria-infected erythrocytes. ICAM-1 expression is predominantly transcriptionally regulated. The ICAM-1 promoter contains several enhancer elements, among them a novel kappa B element which mediates effects of 12-O-tetradecanoylphorbol-13-acetate, interleukin-1, lipopolysaccharide, tumor necrosis factor-alpha, and glucocorticoids. Expression regulation is cell specific and depends on the availability of cytokine/hormone receptors, signal transduction pathways, transcription factors, and posttranscriptional modification. ICAM-1 plays a role in inflammatory processes and in the T-cell mediated host defense system. It functions as a costimulatory molecule on antigen-presenting cells to activate MHC class II restricted T-cells, and on other cell types in association with MHC class I to activate cytotoxic T-cells. ICAM-1 on endothelium plays an important role in migration of (activated) leukocytes to sites of inflammation. ICAM-1 is shed by the cell and detected in plasma as sICAM-1. Regulation and significance of sICAM-1 are as yet unclear, but sICAM-1 is increased in many pathological conditions. ICAM-1 may play a pathogenetic role in rhinovirus infections. Derangement of ICAM-1 expression probably contributes to the clinical manifestations of a variety of diseases, predominantly by interfering with normal immune function. Among these are malignancies (e.g., melanoma and lymphomas), many inflammatory disorders (e.g., asthma and autoimmune disorders), atherosclerosis, ischemia, certain neurological disorders, and allogeneic organ transplantation. Interference with ICAM-1 leukocyte interaction using mAbs, soluble ICAM-1, antisense ICAM-1 RNA, and in the case of melanoma mAb-coupled immunotoxin, may offer therapeutic possibilities in the future. Integration of knowledge concerning membrane-bound and soluble ICAM-1 into a single functional system is likely to contribute to elucidating the immunoregulatory function of ICAM-1 and its pathophysiological significance in various disease entities.
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PMID:Intercellular adhesion molecule-1. 883 67

To evaluate whether atherosclerosis may be associated with altered leucocyte rheology, we assessed leucocyte count (by Coulter counter), aggregation (by means of the leukergy test) and expression of adhesion molecules integrin LFA-1 and CD 44 (by means of immunofluorescence staining and flow cytometry) in 9 patients with carotid plus lower limb artery atherosclerosis (group A), 14 patients with carotid atherosclerosis only (group B) and 23 controls without atherosclerosis (group C). The level of LFA-1 (calculated as mean fluorescence channels-MFCs) on neutrophils, lymphocytes and monocytes was significantly higher (p < 0.05) in group A and B patients than in controls (group A-mean +/- SE: 383.77 +/- 9.42 vs 295.45 +/- 5.76; 474.22 +/- 8.86 vs 388.35 +/- 7.84; 457.66 +/- 12.03 vs 396.25 +/- 4.37. Group B: 322.42 +/- 6.36 vs 295.45 +/- 5.76; 421.42 +/- 7.21 vs 388.35 +/- 7.84; 415.71 +/- 7.73 vs 396.25 +/- 4.37, respectively); furthermore, the MFC of LFA-1 on neutrophils was significantly different (p < 0.05) between group A and B patients. The percentage of aggregated leucocytes was significantly higher (p < 0.05) in group A patients (4.46 +/- 1.07) than those in groups B (1.75 +/- 0.38) and C (1.43 +/- 0.25), whereas no significant difference was detected between groups B and C. Leucocyte number and expression of CD44 were not significantly different among the 3 groups. In conclusion, changes in leucocyte rheology are present in patients with atherosclerosis and may contribute to chronic ischaemia.
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PMID:Leucocyte rheological properties are altered in patients with diffuse atherosclerosis. 924 34

One of the most important events in the reaction to all forms of injury is adhesion of leukocytes to endothelium, a prelude to their emigration into tissues. This process is central to inflammation, atherosclerosis, and immune reactions. Endothelial-leukocyte adhesion is governed largely by the interaction of complementary adhesion molecules on endothelia and leukocytes. The synthesis, surface expression, and avidity of these molecules, are regulated by chemical mediators, particularly chemokines. The most important adhesion molecule pairs are the selectins (E, L and P), the immunoglobulins ICAM-1 and VCAM-1, and the beta 2 and beta 1 integrins (e.g., LFA-1 and VLA-4). In vivo studies in experimental animals and humans have confirmed a role for these molecules in a number of pathological processes, including transplant rejection, septic shock, atherosclerosis, late phase hypersensitivity reactions, immunologically-mediated lung and kidney disease, and reperfusion injury. Besides their importance in understanding pathogenesis, work on adhesion molecules has direct clinical implications in diagnosis and therapy. Current studies suggest that the expression of these adhesion molecules may be a useful marker for active inflammation under certain conditions, and that abrogation of endothelial adhesion by interfering with such molecules may inhibit tissue injury. Mice genetically deficient in adhesion molecules (knock out) have been particularly useful in the study of the role of these molecules in vivo. This lecture will first summarize the state-of the-art on the structure, localization, and distribution of the major adhesion molecules, examine their roles in vivo, in humans and knock-out mice, and point to possible use of the information derived from these studies in diagnosis and therapy.
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PMID:Endothelial adhesion molecules in health and disease. 976 11

The adherence of blood monocytes to the endothelium, followed by transmigration beneath the endothelium, are initiating events in the formation of foam cells, promoting atherogenesis. We showed that adhesion molecules on leukocytes were up- or down-regulated in atherosclerosis, when binding of monoclonal antibodies was measured by indirect immunofluorescence with flow cytometry. Expression of PE-CAM-1 (CD31) on monocytes and LFA-1 (CD11a) on lymphocytes was increased with age. Expression of PECAM-1 in monocytes was also up-regulated in patients with coronary artery disease. Being unchanged on aging, expression of HAR (CD44) on polymorphonuclear leukocytes and monocytes was increased in patients with coronary artery disease. On the other hand, expression of L-selectin (CD62L) on polymorphonuclear leukocytes, and LFA-1, CR3 (CD11b) and VLA-4 (CD49d) on monocytes was decreased. These findings may show the mechanism of increased chemotaxis of monocytes beneath the endothelium during the incipient stage of atherosclerosis.
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PMID:[Adhesion of leukocytes to endothelial cells in atherosclerosis]. 986 1

Recent investigations have reanimated the view that there exists a possible link between atherosclerosis and inflammation. Adhesion of monocytes as well as T lymphocytes to the arterial endothelial surface, followed by their migration into the subendothelial space is a hallmark for experimental animals fed an atherogenic diet. Human studies show identical features in the arterial wall to the animal models of atherosclerosis. The recruitment of leukocytes into areas of inflammation is mediated by interacting sets of cell adhesion molecules. In atherosclerosis, focal expression of key adhesion molecules particularly triggered by plasma atherogenic lipoproteins has been detected, and these molecules may mediate the recruitment of mononuclear cells to the plaque. Among these adhesion molecules, ICAM-1, a protein of the Ig superfamily, and one of the ligands for LFA-1 have been suggested to play an important role in atherogenesis. In diet-induced hypercholesterolemic rats, we found that ICAM-1 expression is up-regulated mainly in lesion-prone areas of the aorta during the early stages of atherogenesis. Increased ICAM-1 expression was associated with a marked monocyte and T lymphocyte intimal recruitment. Further immunohistochemical studies have demonstrated that LFA-1 is expressed by more than 85% of macrophages in the lesions, and their presence therefore may point toward the involvement of the LFA-1/ICAM-1 receptor ligand pathway in the recruitment of mononuclear cells in the lesions. In order to verify this hypothesis, systemic administration of blocking antibodies was attempted; injection of anti-ICAM-1/LFA-1 monoclonal antibodies significantly reduced macrophage adherence and their emigration into the intima. Our current study suggests that ICAM-1 may act as an "athero-ELAM" for mononuclear cell intimal recruitment during atherogenesis.
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PMID:Atherosclerosis and inflammation mononuclear cell recruitment and adhesion molecules with reference to the implication of ICAM-1/LFA-1 pathway in atherogenesis. 995 2

Inflammatory and immune responses are highly relevant processes in the pathogenesis of atherosclerosis, as illustrated by the central event of monocyte accumulation in atherosclerotic plaques. Integrin LFA-1-mediated adhesion of circulating monocytes to the endothelium is a prerequisite for recruitment of monocytes to these areas. Integrin-mediated adhesion is tightly regulated and integrins are only functional in response to particular monocyte activation stimuli. We investigated the role of oxidized low-density lipoprotein (LDL) in adhesion of resting monocytes prepared by elutriation from endothelium. Our results showed that: (1) oxidized LDL (and MCP-1) induced both LFA-1-mediated adhesion of monocytes to endothelial cells and transendothelial migration of monocytes; (2) oxidized LDL functionally transformed monocyte LFA-1 to an activated form; (3) oxidized LDL induced F-actin polymerization and cytoskeletal rearrangement within seconds; and (4) the LDL-associated antioxidant, alpha-tocopherol, but not beta-tocopherol, inhibited both F-actin polymerization and LFA-1-mediated adhesion of monocytes, which paralleled the effect of protein kinase C (PKC) inhibitors. Our results indicate that oxidized LDL plays a pivotal role in triggering LFA-1 activation and LFA-1-mediated adhesion and transmigration of monocytes to sites of atherosclerotic plaques, via the PKC pathway.
Atherosclerosis 2002 Feb
PMID:Oxidized low density lipoprotein-induced LFA-1-dependent adhesion and transendothelial migration of monocytes via the protein kinase C pathway. 1184 49

Physical exercise can affect the risk of cardiovascular disease. Oxidized-low density lipoprotein (ox-LDL) promotes transendothelial migration (TEM) of monocyte, thereby accelerating the pathogenesis of atherosclerosis. This study investigated how exercise intensity affects monocyte/EC interactions under ox-LDL-mediated condition. Light- (LIE), moderate- (MIE) and high- (HIE) intensity exercise (i.e., 40%, 60%, and 80% VO2max, respectively) on a bicycle ergometer in 18 sedentary healthy men were performed on three separate occasions. Before and immediately after exercise, ox-LDL-promoted expressions of monocyte adhesion molecules and TEM of monocyte, as well as oxidation of LDL and amounts of soluble adhesion molecules in plasma were measured. Analytical results showed that (1) ox-LDL furthered monocyte L-selectin shedding and Mac-1 expression, and an attendant increase in TEM of monocyte, while treating the monocyte with Mac-1 antibody inhibited the ox-LDL-promoted TEM of monocyte; (2) under ox-LDL-treated condition, MIE increased monocyte Mac-1 and LFA-1 expressions, enhancing the TEM of monocyte, whereas HIE downregulated monocyte Mac-1 expression, suppressing the TEM of monocyte; (3) LIE decreased basal LFA-1 expression as well as basal and ox-LDL-promoted TEM of monocyte; and (4) MIE and HIE, but not LIE, elevated plasma ox-LDL level, while there were no significant changes in sL-selectin, sE-selectin, sICAM-1, and sVCAM-1 following these exercises. Therefore, we conclude that monocyte activation and subsequent TEM promoted by ox-LDL are changed by short-term exercise in an intensity-dependent manner. These findings provide a new insight into the may aid the development of suitable exercise intensity enable people to prevent early atherogenesis.
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PMID:Exercise paradoxically modulates oxidized low density lipoprotein-induced adhesion molecules expression and trans-endothelial migration of monocyte in men. 1627 Jun 41


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