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)

A critical event in the early stages of atherosclerosis is the focal accumulation of lipid-laden foam cells derived from macrophages. In various cholesterol-fed animal models of atherosclerosis, localized attachment of circulating monocytes to arterial endothelial cells appeared to precede the formation of foam cells. It is suggested that monocyte recruitment into early lesions depends on the endothelial adhesiveness for monocytes and lymphocytes. In vivo and in vitro experiments have identified molecules, such as ICAM-1, VCAM-1, and P-selectin, that can support the adhesion of monocytes and lymphocytes. Moreover, oxidized LDL, lysophosphatidyl-choline, and oxidized fatty acids induce the expression not only of these adhesion molecules but also of scavenger receptors, such as CD-36, SR-A, and LOX-1. Recently, we isolated and characterized the novel receptors for oxidized LDL, namely, LOX-1 and SR-PSOX. Expression of LOX-1 is found on endothelial cells, smooth muscle cells, and macrophages, whereas SR-PSOX is expressed on macrophages. In this paper the significance of oxidized LDL and its receptors, LOX-1 and SR-PSOX, in terms of atherogenesis is discussed.
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PMID:Role of oxidized LDL in atherosclerosis. 1179 67

One of the critical events in the early stage of atherosclerosis is the focal accumulation of lipid-laden foam cells derived from macrophages. In various cholesterol-fed animal models of atherosclerosis, it was found that localized attachment of circulating monocytes to arterial endothelial cells appears to precede the formation of foam cells. It has been suggested that monocyte recruitment into early lesions is depend upon the endothelial adhesiveness for monocytes and lymphocytes. In vivo and in vitro experiments have identified molecules, such as ICAM-1, VCAM-1 and P-selecin, those can support the adhesion of monocytes and lymphocytes. Moreover oxidized LDL, lysophosphatidylcholine and oxidized fatty acids induce the expression of not only these adhesion molecules but also scavenger receptors, such as CD-36, SR-A and LOX-1. Recently we isolated and characterized the novel receptors for oxidized LDL, named LOX-1 and SR-PSOX. The expression of LOX-1 is found on endothelial cells, smooth muscle cells and macrophages. Whereas SR-PSOX expresses on macrophages. We address in this paper on the significance of hyperlipidemia, especially oxidized LDL and its receptors in terms of atherosclerosis.
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PMID:[Hyperlipidemia and atherosclerosis]. 1202 85

Atherosclerosis is an inflammatory disease of the vessel wall, characterized by the accumulation of leukocytes, especially macrophages and T-cells. Chemokines are small heparin-binding polypeptides, whose main function is to attract cells to the areas of developing inflammation. They function by ligating G-protein coupled chemokine receptors initiating different signaling cascades. In vivo and in vitro investigations showed that chemokines are produced by a variety of cells and play important roles in the development and progression of many physiological and pathological conditions including atherosclerosis. Chemokines such as MCP-1, MCP-4, MIP-1 and RANTES may mediate leukocyte trafficking to, and their retention in, the plaque while CXCL16 seems to fulfill the dual function of a chemokine and a scavenger receptor. Chemokine and chemokine receptor homologues are secreted by several viruses, which may also play a role in the pathogenesis of atherosclerosis. Expression levels and gene polymorphisms of some chemokines may become useful clinical markers of atherosclerosis and other cardiovascular diseases. Modulation of chemokines and chemokine receptors' expression as well as their signaling pathways may provide important anti-atherogenic strategies.
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PMID:Chemokines and atherosclerosis. 1511 30

Atherosclerosis is an inflammatory disease that is characterised by the involvement of chemokines that are important for the recruitment of leukocytes and scavenger receptors that mediate foam cell formation. Several cytokines are involved in the regulation of chemokines and scavenger receptors in atherosclerosis. CXCL16 is a chemokine and scavenger receptor and found in macrophages in human atherosclerotic lesions. Using double-labelled immunohistochemistry, we identified that smooth muscle cells in human lesions express CXCL16. We then analysed the effects of IFN-gamma, TNF-alpha, IL-12, IL-15, IL-18, and LPS on CXCL16 expression in cultured aortic smooth muscle cells. IFN-gamma was the most potent CXCL16 inducer and increased mRNA, soluble form, membrane form, and total cellular levels of CXCL16. The IFN-gamma induction of CXCL16 was also associated with increased uptake of oxLDL into these cells. Taken together, smooth muscle cells express CXCL16 in atherosclerotic lesions, which may play a role in the attraction of T cells to atherosclerotic lesions and contribute to the cellular internalisation of modified LDL.
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PMID:The chemokine and scavenger receptor CXCL16/SR-PSOX is expressed in human vascular smooth muscle cells and is induced by interferon gamma. 1555 52

Foam cell formation from macrophages with subsequent fatty streak formation plays a key role in early atherogenesis. Foam cell formation is thought to be induced by Low Density Lipoproteins (LDL), including oxidized LDL (OxLDL) or minimally modified LDL (mmLDL). Understanding the molecular mechanisms involved in OxLDL- and mmLDL-induced foam cell formation is of fundamental importance for atherosclerosis and cardiovascular disease. The expression of many genes is likely modulated during macrophage transformation into a foam cell. In this mini-review we describe functional consequences of modulation of three groups of genes: Scavenger Receptors (SR-A, CLA-1/SR-BI, CD36, CD68, LOX-1, and SR-PSOX), the PPAR family of nuclear receptors, and a number of genes involved in eicosanoid biosynthesis, including lipoxygenases and leukotriene receptors. Scavenger receptors appear to play a key role in uptake of OxLDL, while mmLDL appears to interact with CD14/TLR4. The regulation of scavenger receptors is, in part, mediated by the PPAR family of nuclear receptors. PPARalpha and PPARgamma agonists, such as thiazolidinediones and fibrates, and PPARdelta agonists were tested as atheroprotective drugs and showed some beneficial effects. Eicosanoids are naturally occuring agonists for PPARs. Recent observations indicate a role of the components of the eicosanoid cascade, such as 5-lipoxygenase, 15-lipoxygenase and the leukotriene receptors in foam cell formation. Selective inhibitors of lipoxygenases and leukotriene receptors could be useful in the treatment of atherosclerosis by preventing or reducing foam cell formation.
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PMID:Macrophage differentiation to foam cells. 1617 64

Unregulated uptake of oxidized low-density lipoproteins (ox-LDL) via macrophage scavenger receptors (SRs) such as lectin-like ox-LDL receptor-1 (LOX-1) is a key event in atherosclerosis. In this study, we examined the effects of five selected food phytochemicals on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced LOX-1 mRNA expression in THP-1 human monocyte-like cells. Nobiletin, a citrus polymethoxylated flavone, markedly reduced it in dose- and time-dependent manners. It also suppressed the phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2, c-Jun NH2-terminal kinase (JNK) 1/2, and c-Jun (Ser-63), thereby inhibiting the transcriptional activity of activator protein-1. Further nobiletin attenuated expression of SR-A, SR-PSOX, CD36, and CD68, but not CLA-1, mRNA, leading to the blockade of DiI-acLDL uptake. Together, our results suggest that nobiletin is a promising phytochemical for regulating atherosclerosis with reasonable action mechanisms.
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PMID:Nobiletin, a citrus flavonoid, suppresses phorbol ester-induced expression of multiple scavenger receptor genes in THP-1 human monocytic cells. 1669 17

CXCL16 is a transmembrane non-ELR CXC chemokine that signals via CXCR6 to induce aortic smooth muscle cell (ASMC) proliferation. While bacterial lipopolysaccharide (LPS) has been shown to stimulate CXCL16 expression in SMC, its effects on CXCR6 are not known. Here, we demonstrate that LPS upregulates CXCR6 mRNA, protein, and surface expression in human ASMC. Inhibition of TLR4 with neutralizing antibodies or specific siRNA interference blocked LPS-mediated CXCR6 expression. LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-kappaB (p50 and p65) activation, but only inhibition of AP-1 attenuated LPS-induced CXCR6 expression. Using dominant negative expression vectors and siRNA interference, we demonstrate that LPS induces AP-1 activation via MyD88, TRAF6, ERK1/2, and JNK signaling pathways. Furthermore, the flavoprotein inhibitor diphenyleniodonium chloride significantly attenuated LPS-mediated AP-1-dependent CXCR6 expression, as did inhibition of NOX4 NADPH oxidase by siRNA. Finally, CXCR6 knockdown inhibited CXCL16-induced ASMC proliferation. These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis.
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PMID:TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells. 1687 Jan 45

CXCL16 acts as a scavenger receptor for oxLDL in its membrane-bound form and induces migration of activated T cells in its soluble form. Due to these properties, CXCL16 has been suggested to play a role in both atherosclerosis and rheumatoid arthritis (RA). Our aim was to evaluate the contribution of soluble CXCL16 to the scavenging of oxLDL and its potential as a marker for cardiovascular disease (CVD) in patients with RA. We found that circulating CXCL16 was not correlated with plasma oxLDL or ApoB and was not related to the presence of CVD in RA patients. Moreover, CXCL16 did not bind and scavenge oxLDL in an in vitro setting. These data suggest that binding of oxLDL by soluble CXCL16 does not play a role in atherosclerosis and, although confirmation in larger studies is needed, that circulating CXCL16 is not related to the presence of CVD in patients with RA.
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PMID:Circulating CXCL16 is not related to circulating oxLDL in patients with rheumatoid arthritis. 1730 Jul 46

The aim of this study is to construct a lentiviral expression vector containing a scavenger receptor (SR-PSOX) that binds with uniquely phosphatidylserine and oxidized lipoprotein with six histidine tags and to investigate the function of SR-PSOX in atherosclerosis. We utilize the ViraPower lentiviral expression system which was efficient to deliver in vitro or in vivo the target gene into dividing and non-dividing mammalian cells using an enhanced biosafety replication-incompetent lentivirus. The blunt-end sequence was amplified using the reverse transcription-polymerase chain reaction and directional TOPO cloning reaction. Through a pair of the cytomegalovirus forward primer and the reverse primer of SR-PSOX, the correct clones were identified by polymerase chain reaction and sequencing. The ViraPower packaging mix and SR-PSOX-pLenti6/V5 TOPO expression plasmid were co-transfected into the 293FT cell line using Lipofectamine 2000. The expression of endogenous and exogenous SR-PSOX as well as tumor necrosis factor (TNF)-alpha protein in various foam cell models at different time points were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blot and indirect immunofluorescence assay. Western blot and immunofluorescence analysis confirmed that the expressions of SR-PSOX and TNF-alpha protein were upregulated in foam cell models. Our data suggested that the overexpression of recombinant human SR-PSOX protein can promote foam cell formation and upregulate the expression of the inflammatory factor TNF-alpha.
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PMID:Construction and functional analysis of a lentiviral expression vector containing a scavenger receptor (SR-PSOX) that binds uniquely phosphatidylserine and oxidized lipoprotein. 1734 60

Unregulated uptake of oxidized low-density lipoproteins (ox-LDL) via macrophage scavenger receptors (SRs), such as lectin-like ox-LDL receptor-1 (LOX-1), is a key event in atherosclerosis. In the present study, we used differentiated Caco-2 cells as a model of the human small intestine to evaluate the suppressive effects of 16 traditional food items selected from Okinawa on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced LOX-1 mRNA expression in THP-1 human monocyte-like cells. Three Zingiberaceae plants, Curcuma aromatica Salisbury, Curcuma longa L., and Zingiber zerumbet Smith, markedly suppressed that expression. When added to the apical sides of Caco-2 monolayers, zerumbone, a sesquiterpene from Z. zerumbet Smith, was found to permeate into the basolateral medium as an intact structure in a time-dependent manner. alpha-Humulene, a structural analog of zerumbone lacking the alpha,beta-unsaturated carbonyl group, did not suppress LOX-1 mRNA expression, indicating that its electrophilic moiety might play pivotal roles in its activities. Further, zerumbone attenuated the expression of SR-A, SR-PSOX, and CD36, but not that of CD68 or CLA-1, leading to a blockade of DiI-acLDL uptake, while it also inhibited the transcriptional activities of activator protein-1 and nuclear factor-kappaB. Together, our results indicate that zerumbone is a potential phytochemical for regulating atherosclerosis with reasonable action mechanisms.
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PMID:Zerumbone suppresses phorbol ester-induced expression of multiple scavenger receptor genes in THP-1 human monocytic cells. 1742 Jun 7


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