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)

Leukocytes play some important roles in pathophysiological conditions, such as inflammation, atherosclerosis, etc. It has been known that adhesion of leukocytes to vascular endothelial cells is the initial step in these conditions. Leukocytes adhere to endothelial cells utilizing adhesion molecules, such as CD11/CD18-I CAM-1, sialyl Lewis X-ELAM-1, etc. In this paper. The structure, expression and function of ICAM-1 and ELAM-1 on the endothelium is explained. ICAM-1 is a 90 kd inducible surface glycoprotein that belongs to the immunogloblinsuperfamily. Expression of ICAM-1 on the endothelium exposed to TNF, IL-1, LPS and IFN-gamma increase. This expression peaks at about 24 hours. ICAM-1 binds to CD11a/CD18 on the surface of leukocytes and takes part in the transendothelial migration. ELAM-1 is a 115 kd inducible glycoprotein, that consists of one lectin domain, one EGF-like domain and six complement regulatory like molecules. Endothelial cells will express ELAM-1 following stimulation by TNF, IL-1 and LPS. This expression peaks at 4-6 hours, declines at 24 hours. ELAM-1 binds to sialyl Lewis X on the leukocytes and participates in the rolling phenomenon, the first step of adherence to endothelium. Clarification of the mechanism of adhesion molecules expression may facilitate the treatment and prevention of vascular diseases.
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PMID:[Molecular biology of adhesion molecules--structure, expression and function of ICAM-1 and ELAM-1]. 768 87

Recent studies suggest the involvement of inflammatory mechanisms in the progression of atherosclerosis. Cysteinyl leukotrienes and cytokines could orchestrate this progression by acting on the proliferation of vascular smooth muscle cells (VSMC). In cultures of rat VSMC, proliferation was modulated by cysteinyl leukotriene C4 (LTC4) and LTD4, but not LTE4. Co-culturing LTD4 with VSMC produced an increased cell proliferation as assessed by [3H]thymidine incorporation studies (200%) as well as cell counts (70%), using LTD4 at 10(-6)M compared to controls. LTD4 exerted its effect through an interleukin 1 (IL-1)-dependent autocrine regulatory mechanism. When IL-1 was inhibited by using a receptor antagonist (IL-1ra) and a polyclonal antibody to IL-1, we found an inhibition of VSMC proliferation. The increase of VSMC proliferation was associated with the autocrine production of interleukin-1 (IL-1) concomitant to LTD4 stimulation (55.5 +/- 2.5 pg/ml in controls and 177 +/- 0.5 pg/ml in 10(-6)M LTD4). These results may shed new light on the mechanism of inflammatory involvement during atherogenesis, suggesting that the control of cysteinyl leukotrienes may be important in inflammatory processes involving IL-1.
Atherosclerosis 1995 Feb
PMID:Modulation of rat vascular smooth muscle cell (VSMC) proliferation by cysteinyl leukotriene D4: a role for mediation of interleukin 1. 775 46

The present study demonstrates for the first time that iron ions can induce lipid peroxidation in intact macrophages without causing cell death. Macrophage lipid peroxidation increases cell-mediated oxidation of LDL, enhances the release of interleukin 1 and inhibits the release of apolipoprotein E from the macrophages. When cultured macrophages were exposed to ferrous ions (50 microM FeSO4) for 4 h at 37 degrees C, cellular lipid peroxidation (measured by analyses of malondialdehyde (MDA), conjugated dienes (CD), and lipid peroxides (PD)) increased 2-4-fold in comparison with non-treated cells. This process was iron-dose dependent, reached its maximum after 4 h of incubation, and was accompanied by 68% and 53% reductions in the content of the cellular linoleic (18:2), and arachidonic acid (20:4), respectively, and by 29% and 36% reductions of cellular vitamin E and vitamin A, respectively. Cell viability (measured by trypan blue exclusion, by [3H]thymidine incorporation into DNA, by analysis of the release of lactate dehydrogenase (LDH) or [3H]adenine), and cell morphology (studied by scanning electron microscopy) were not significantly affected by the iron-induced oxidative stress. Manitol and dimethylthiourea (DMTU), but not catalase or superoxide dismutase (SOD), significantly inhibited iron-induced cellular lipid peroxide formation, suggesting that hydroxyl radical, but not superoxides or hydrogen peroxides, mediated the iron-induced cellular lipid peroxidation. Incubation of LDL (0.2 mg of protein/ml) with oxidized macrophages resulted in LDL lipids peroxidation, as evidenced by an 8-fold increase in the LDL associated MDA in comparison with LDL that was incubated under similar conditions with non-oxidized macrophages. Furthermore, oxidation of LDL by oxidized macrophages in the presence of copper ions (10 microM CuSO4) was 2-fold higher in comparison with oxidation of LDL by non-oxidized macrophages. The release of apolipoprotein E from oxidized macrophages decreased by 50%, whereas macrophage release of beta-glucuronidase and of interleukin-1 beta increased by 83% and by a factor of 6, respectively. This study demonstrates for the first time that iron ions induce oxidation of the cellular polyunsaturated fatty acids in intact macrophages and that this cellular lipid peroxidation can subsequently induce LDL oxidation.
Atherosclerosis 1994 Nov
PMID:Iron induces lipid peroxidation in cultured macrophages, increases their ability to oxidatively modify LDL, and affects their secretory properties. 784 Aug 15

Infiltration of mononuclear cells is an early pathological finding in human and experimental atherosclerosis. However, the cellular and molecular basis for cell infiltration is incompletely understood. While the intercellular adhesion molecule-1 (ICAM-1) is expressed on endothelial cells and promotes the adhesion of mononuclear cells, there is little information on the expression of ICAM-1 on vascular smooth muscle cells (SMC). In this study, we investigated the expression of ICAM-1 on cultured rat SMC and its regulation by pro-inflammatory cytokines, interleukin 1 alpha (IL-1 alpha), interleukin 6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1). In immunohistochemical staining, ICAM-1 molecules were constitutively expressed on the surface of SMC. In flow cytometric and ELISA analyses, ICAM-1 molecule expression on SMC was significantly upregulated by IL-1 alpha and MCP-1, but not by IL-6, in a dose-dependent manner. The effects of IL-1 alpha and MCP-1 were observed as early as 4 h. In Northern blot analysis, ICAM-1 mRNA was slightly detectable in unstimulated SMC, but its expression was clearly observed following exposure to IL-1 alpha or MCP-1. These results suggest that ICAM-1 on SMC, as well as on endothelial cells, could participate in the focal accumulation of mononuclear cells in human atherosclerotic lesions.
Atherosclerosis 1993 Dec
PMID:Expression of intercellular adhesion molecule-1 on rat vascular smooth muscle cells by pro-inflammatory cytokines. 790 95

The possible involvement of immunological mechanisms in the pathogenesis of atherosclerosis has been suggested intermittently since the early 1970s. Both humoral and cellular mechanisms have been proposed to participate in the onset and/or progression of atheromatous lesions, but the theories postulating the involvement of autoantibodies and immune complexes have met with considerable experimental support. Modified lipoproteins, particularly different forms of oxidized LDL, have been reported to elicit humoral immune responses in both experimental animals and humans. Oxidized LDL has been demonstrated in atheromatous lesions, anti-oxidized LDL antibodies have been detected in circulation and in atheromatous plaques, and immune complexes formed with LDL and anti-LDL have been isolated from the serum of patients with manifestations of atherosclerosis. In addition, in vitro-formed LDL-IC and IC isolated from patients have been demonstrated to cause intracellular accumulation of cholesteryl esters (CE) in human macrophages and fibroblasts. The accumulation of CE in macrophages exposed to LDL-IC is unique to this type of IC and is associated with a paradoxical overexpression of the native LDL receptor and with increase synthesis and release of interleukin 1 and TNF-alpha. The release of these cytokines in the subendothelial space may have a significant role in promoting the interaction of endothelial cells with mononuclear cells, causing endothelial cell damage directly or indirectly, and also in inducing smooth muscle cell proliferation. Thus, several lines of evidence suggest that humoral autoimmunity may play a significant role in the pathogenesis of atherosclerosis.
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PMID:Atherosclerosis and autoimmunity. 792 23

The adherence of monocytes to the endothelium is an early event in atherogenesis. Our previous studies have demonstrated that oxidized LDL induced U937 cells-endothelial interactions and that HDL prevented oxidized LDL effects. Here, we provide evidence that treatment of endothelial cells with the anti-inflammatory agent indomethacin abolished oxidized LDL as well as interleukin 1- and lipopolysaccharide-stimulated U937 adhesion. It is noteworthy that HDL, which is known to be protective against atherosclerosis, was effective only in negating U937 adhesion induced by oxidized LDL, while it did not affect interleukin 1- and lipopolysaccharide-induced hyperadhesiveness in endothelial cells. Since indomethacin inhibits cyclooxygenase which is the key enzyme in the synthesis of prostanoids, we have studied the effect of oxidized LDL on the expression of cyclooxygenase type 2 and demonstrated that oxidized LDL induces a sustained increase in the expression of cyclooxygenase mRNA.
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PMID:Modulators of oxidized LDL-induced hyperadhesiveness in human endothelial cells. 798 May 28

It has been proposed for several decades that infections may be responsible for the accelerated development of atherosclerosis. Numerous studies have shown an association between atherosclerosis and both viral and bacterial infections. In this review, we summarize the evidence linking infections with abnormalities in lipid and lipoprotein levels and the role of cytokines in mediating these abnormalities. We have also summarized the effects of the interaction between LDL and lipopolysaccharides (LPS) on lipoprotein metabolism and their possible contributing role to the development of atherosclerosis; the possible role of LPS in inducing endothelial cell damage and in stimulating the oxidative metabolism of monocytes, leading to the release of superoxide anion (O2-) and to the oxidation of LDL. Oxidatively modified LDL has, in recent years, been implicated as a contributing factor in the development of atherosclerosis, due to its ability to induce the transformation of macrophages into foam cells, to promote monocyte binding to the endothelium and to act as a potent chemo-attractant for circulating human monocytes. Furthermore, oxidized-LDL is immunogenic and thus, it can induce the production of antibodies and subsequent formation of immune complexes. These immune complexes, when taken up by macrophages through the Fc receptor, induce a marked accumulation of cholesteryl esters in these cells and also promote their activation and the subsequent release of cytokines, such as interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF alpha). In addition to the effects that IL-1 and TNF alpha seem to have on lipid and lipoprotein levels, they induce adherence of leukocytes to endothelial cells by promoting the expression of several specific cell adhesion molecules; they can also elicit synthesis and cell surface expression of procoagulant activity in endothelial cells and cause an increase in vascular permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interactions between bacterial lipopolysaccharides and serum lipoproteins and their possible role in coronary heart disease. 813 79

Altered lipoprotein metabolism and vascular injury are considered to be major parts of the pathogenesis of atherosclerotic lesions. Serum amyloid A (SAA) is a family of acute-phase reactants found residing mainly on high density lipoproteins (HDL) in the circulation. Several functions for the SAAs have been proposed that could be important in atherosclerosis. These include involvement in cholesterol metabolism, participation in detoxification, depression of immune responses, and interference with platelet functions. Like other acute-phase reactants, the liver is a major site of SAA synthesis. However, studies in the mouse have revealed that several cell types including macrophages express SAA. Furthermore, we recently found that SAA mRNA expression can be induced in the human monocyte/macrophage cell line, THP-1. In the present study, human atherosclerotic lesions of coronary and carotid arteries were examined for expression of SAA mRNA by in situ hybridization. Surprisingly, SAA mRNA was found in most endothelial cells and some smooth muscle cells as well as macrophage-derived "foam cells," adventitial macrophages, and adipocytes. In addition, cultured smooth muscle cells expressed SAA1, SAA2, and SAA4 mRNAs when treated with interleukin 1 or 6 (IL-1 or IL-6) in the presence of dexamethasone. These findings give further credence to the notion that the SAAs are involved in lipid metabolism or transport at sites of injury and in atherosclerosis or may play a role in defending against viruses or other injurious agents such as oxidized lipids. Furthermore, expression of SAAs by endothelial cells is compatible with the evidence that SAA modulates platelet aggregation and function and possibly adhesion at the endothelial cell surface.
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PMID:Expression of apolipoprotein serum amyloid A mRNA in human atherosclerotic lesions and cultured vascular cells: implications for serum amyloid A function. 815 22

Congenital nephrotic syndrome of the Finnish type (CNF) is well characterized in infants and associated with major lipid risk factors for atherosclerosis. This study was undertaken to investigate if any arterial pathology is present in children with CNF and, if so, to describe its nature in renal arteries collected at nephrectomy at a mean age of 12.5 +/- 4.4 months. Denuded endothelial injury and intimal thickening were seen in 9 out of 10 patient specimens of renal arteries. Intimal thickening contained loose abundant extracellular matrix with a few smooth muscle or myofibroblastoid cells. Only a few Sudan black- or oil red O-positive lipid droplets were found in six and seven samples, respectively. Areas immunoreactive with antibodies against apoprotein B were seen in only two specimens. Immunohistochemistry did not reveal any activated T or B cells, or any expression of IL-1 or IL-2 receptors. Macrophages were present in only two specimens. No foam cells were seen. We conclude that the vascular pathology together with altered lipoprotein metabolism indicates that children with CNF might be at risk for early atherosclerotic arterial disease, particularly if their hyperlipidemia persists.
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PMID:Pathology of renal arteries of dyslipidemic children with congenital nephrosis. 816 9

We previously demonstrated that C-type natriuretic peptide (CNP), originally isolated from the porcine brain, is produced by endothelial cells and proposed that CNP can exert local control over vascular tone and growth as a local regulator from endothelial cells. Since cytokines play pivotal roles in the control of vascular tone and structure, we have examined effects of various cytokines on CNP secretion from endothelial cells using the specific radioimmunoassay for CNP. While interleukin (IL)-2 had no significant effect on CNP secretion, IL-1 alpha, IL-1 beta and tumor necrosis factor (TNF)-alpha stimulated CNP secretion in a time- and dose-dependent manner. Among them, TNF-alpha, one of the key mediators for inflammation and vascular remodeling, induced more than two orders of magnitude increase in CNP secretion. In addition, lipopolysaccharide (LPS) potently stimulated CNP secretion. These results indicate that IL-1, TNF-alpha and LPS, the endotoxin itself, can regulate local vascular tone and growth through the activation of CNP secretion from endothelial cells. Therefore, CNP could be of clinical relevance as an autocrine/paracrine regulator from endothelial cells for systemic and local cytokine-associated disorders, such as endotoxin shock and atherosclerosis.
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PMID:Cytokine-induced C-type natriuretic peptide (CNP) secretion from vascular endothelial cells--evidence for CNP as a novel autocrine/paracrine regulator from endothelial cells. 824 33


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