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

The study of the fibrinolytic system and the activity of interleukin 1 and 2 in 75 patients with various cardial manifestations of atherosclerosis (angina of effort, angina decubitus, arrhythmia, symptomatic hypertension) revealed a decrease in the activity of plasminogen--a blood activator--in patients with angina of effort, angina decubitus and cardiac arrhythmias. In those with atherosclerotic hypertension the activatory activity was in the normal limits. A decrease in the activity of interleukin 1 and 2 was noted in all those examined.
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PMID:[Fibrinolysis, interleukins and coronary atherosclerosis]. 150 14

The production of the precursor of tissue collagenase/matrix metalloproteinase 1 (proMMP-1) by cultured human aortic medial smooth muscle cells (SMCs) was significantly enhanced by the treatment of the cells with platelet-derived growth factor (PDGF), interleukin 1 or 12-O-tetradecanoylphorbol-13-acetate (TPA). The response to PDGF of SMCs exhibited a tendency to be age-dependent: only SMCs obtained from older individuals (age: 54, 56, 72 and 74 years) responded to PDGF and synthesized proMMP-1, but not SMCs from young individuals (age: 10, 16 and 41 years), and weak responsiveness with a 19-year-old individual. On the other hand, induction of proMMP-1 synthesis in SMCs by TPA was not discriminated by age. The synthesis of two other related matrix metalloproteinases was also examined. Matrix metalloproteinase 2 was found to be constitutively expressed in zymogen form in SMCs and its synthesis was not affected by the treatments with PDGF, interleukin 1 or TPA. The synthesis of matrix metalloproteinase 3 (stromelysin) was not detected in SMCs from both young and old individuals even after the treatment with PDGF, interleukin-1, prostaglandin E2 or TPA. The ability of SMCs to synthesize and secrete proMMP-1 in response to PDGF suggests that this enzyme plays an important role in the migration of PDGF-stimulated SMCs from the media into the intima of aorta and the eventual formation of atherosclerotic plaques.
Atherosclerosis 1991 Dec
PMID:Production of tissue collagenase (matrix metalloproteinase 1) by human aortic smooth muscle cells in response to platelet-derived growth factor. 166 62

At present, it is known that the immune system acts through the release of protein factors, so-called cytokines. In addition to their immunomodulating and endocrinometabolic effects, cytokines have appeared to be able to have an influence on the cardiovascular system by inducing important haemodynamic changes. Cytokines cause hypotension, particularly IL-2 and TNF, due at least in part to a production of nitric oxide by endothelial cells. Cytokines, such as IL-1, IL-6 and TNF, stimulate myocardial infiltration by activating leukocytes and inducing the release of cytotoxic factors during myocardial infarction; that would extend the area of necrosis. Finally, cytokines would be involved in the pathogenesis of the atherosclerosis, and cholesterol metabolism itself would be under a cytokine control. On these bases, it is possible to suggest in the near future the elaboration of new therapeutic strategies and prognostic indications, according to the bioimmunological response of patients with cardiovascular diseases.
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PMID:[Cardioangioimmunology: the immune implications in the principle cardiovascular pathologies]. 180 53

Immediately after a cuff-sheathing of rabbit carotid artery, a large number of leukocytes adhered to injured endothelium then infiltrated into the media. These inflammatory responses were followed by an atherosclerotic change, intimal thickening, of the artery. A simultaneous injection of dexamethasone (10 mg/kg i.m.) inhibited the leukocyte accumulation by 74% when evaluated 18 h thereafter. Similarly, 39% inhibition was obtained with the same dose of FR110302, a potent 5-lipoxygenase inhibitor. On the other hand, the same dose of indomethacin, a cyclooxygenase inhibitor, had little effect on the leukocyte accumulation. The intimal thickening which was evaluated 3 weeks after the cuff-treatment was attenuated by a daily dose (10 mg/kg i.m.) of dexamethasone or FR110302 but not by one of indomethacin. The inhibition by the two former drugs were 91 and 58%, respectively. In vitro, the three drugs in concentrations up to 10 microM hardly affected endothelial adhesion of PMN which was induced by LPS or IL-1. Though 10 microM of FR110302 and indomethacin significantly decreased PMN chemotaxis induced by LTB4, the decreases were less than that at 10 microM dexamethasone. These results confirm a possible linkage between inflammation and atherosclerosis, and suggest that 5-lipoxygenase products contribute to the initiation and development of atherosclerosis.
Atherosclerosis 1991 Nov
PMID:Role of inflammatory responses in initiation of atherosclerosis: effects of anti-inflammatory drugs on cuff-induced leukocyte accumulation and intimal thickening of rabbit carotid artery. 181 46

Clinical and experimental evidence suggests that shock, arthritis, osteoporosis, colitis, leukemia, diabetes, wasting and atherosclerosis are mediated, in part, by interleukin 1 (IL-1). Inhibition of this cytokine has been a strategy for studying disease and for new drug development. A naturally-occurring IL-1 inhibitor (IL-1 receptor antagonist, IL-1ra) that blocks binding of IL-1 to its receptors has been cloned and produced in recombinant organisms. IL-1ra reduces the severity of sepsis, colitis, arthritis and diabetes in animals and is presently being tested in humans with arthritis, shock and myelogenous leukemia.
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PMID:Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. 183 80

Restenosis after coronary angioplasty is due to a proliferation of smooth muscle cells growing in the vascular lumen, beneath the residual fragments of the atherosclerotic plaque, as seen in necropsy studies and examination of the specimens removed by atherectomy. At the histological analysis thrombi or their fibrocellular organization are not usually detectable. Smooth muscle cell proliferation leading to restenosis is very similar to the one observed in the experimental models of response-to-injury, so that these models are used to investigate into the pathogenetic mechanisms of restenosis. The main stimulus to the loss of the contractile phenotype and to the start of the smooth muscle cell proliferation is represented by the growth factors delivered by platelets adhered to the disendothelialized wall and by the smooth muscle cells themselves, stretched during the dilatation. Other stimuli can be growth factors delivered by monocytes and fibroblasts, by thrombin, endothelin, angiotensin and interleukin 1. The elastic recoil of the vessel wall, the plaque debris and the regional wall shear stress can also contribute to restenosis. The restenosis tissue is different from the atheromatous plaque in that it is almost only constituted by smooth muscle cells and intercellular matrix, while atheroma is much more complex due to the presence of various kinds of cells, of necrotic debris and lipid substances. The smooth muscle cells proliferation also contributes to the pathogenesis of atherosclerosis, but the stimuli starting this process have not been clarified yet; moreover this process is much slower than restenosis, interacting with several factors. Encouraging results have been achieved in the prevention of restenosis after angioplasty in experimental models, but not in man. In order to reduce the incidence of restenosis one should improve the results of angioplasty, even by the use of atherectomy and intracoronary stents. Among pharmacologic approaches anticoagulants, heparin, antiplatelet agents, calcium-channel blockers, corticosteroids all proved ineffective. Studies are in progress evaluating the effect of inhibitors of platelet-derived growth factor (PDGF), antitumor agents and radiation therapy, hirudin, angiotensin-converting enzyme inhibitors and HMG-CoA reductase inhibitors.
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PMID:[Restenosis after coronary angioplasty: its pathogenesis and prevention]. 184 86

The cytokine interleukin-1, IL-1, likely plays an important role in the early stages of atherogenesis. The possible action of probucol and tocopherol on the expression and secretion of IL-1 beta was investigated using the human monocytic leukemia cell line, THP-1. Both probucol and D-alpha-tocopherol inhibit the phorbol ester-induced release of IL-1 beta without altering differentiation. Analysis of IL-1 beta mRNA levels revealed that probucol and tocopherol had an inhibitory effect on the activation of expression of the IL-1 beta gene. The data suggest that the beneficial effects of probucol may be related to inhibition of IL-1 at an early phase of atherosclerotic plaque formation.
Atherosclerosis 1991 Feb
PMID:Inhibition of IL-1 beta expression in THP-1 cells by probucol and tocopherol. 187 19

The present study was designed to investigate the capacity of human vascular smooth muscle cells (SMCs) to produce a cytokine chemotactic for monocytes (monocyte chemotactic protein [MCP]) and by way of comparison, a related polypeptide activator of neutrophils (known as interleukin-8 [IL-8] or neutrophil activating protein-1 [NAP-1]. On exposure to IL-1, SMCs released high levels of chemotactic activity for monocytes, which could be removed by absorption with anti-MCP antibodies. MCP production by activated SMCs was comparable to that of IL-1-stimulated umbilical vein endothelial cells. Activated SMCs released appreciable levels of IL-8, as determined by a specific enzyme-linked immunosorbent assay, but little chemotactic activity for neutrophils. IL-1-treated SMCs expressed high levels of both MCP and IL-8 mRNA transcripts, as assessed by Northern blot analysis. Tumor necrosis factor and bacterial lipopolysaccharide but not IL-6 also induced MCP and IL-8 gene expression in SMCs. Nuclear runoff analysis revealed that IL-1 augmented transcription of the MCP and IL-8 genes. The capacity of SMCs to produce a cytokine (MCP) that recruits and activates circulating mononuclear phagocytes may be of considerable importance in the pathogenesis of vascular diseases (e.g., vasculitis and atherosclerosis) that are characterized by monocyte infiltration of the vessel wall.
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PMID:Expression of monocyte chemotactic protein and interleukin-8 by cytokine-activated human vascular smooth muscle cells. 191 3

The proliferation of vascular smooth muscle cells is controlled by specific growth factors and cytokines acting in paracrine networks. Macrophage products such as the platelet-derived growth factor and interleukin 1 promote smooth muscle proliferation and are released in the arterial wall during atherosclerosis and repair processes. T lymphocytes are also present in vascular tissue, but their role in vascular growth control in vivo has been unclear. We now demonstrate that rats in which T lymphocytes have been eliminated by a monoclonal antibody develop larger proliferative arterial lesions after balloon-catheter injury. Larger lesions also develop in athymic rnu/rnu rats that lack T lymphocytes, when compared with rnu/+ littermates with normal T-cell levels. Finally, injection of the lymphokine interferon gamma inhibits smooth muscle proliferation and results in smaller lesions compared with controls injected with buffer alone. These results indicate that T lymphocytes modulate smooth muscle proliferation during vascular repair. We propose that T lymphocytes may play an important, immunologically nonspecific role in tissue repair processes.
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PMID:T lymphocytes inhibit the vascular response to injury. 196 17


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