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)

Monocyte-derived macrophages play a central role in atherosclerotic lesion formation and potentially plaque destabilization by expression of matrix metalloproteinases (MMPs); however, mechanisms associated with stimulating MMP production are not clearly understood. EMMPRIN, which is expressed by human cancer cells and macrophages, present in human, mouse and rabbit atherosclerosis and noted to induce MMPs may be involved. A DNA fragment containing 1797 bp 5' upstream of the EMMPRIN gene and the transcription start site was generated by polymerase chain reaction and cloned into a luciferase reporter gene vector, pGL3-basic. The relative luciferase activities driven by this 5'-upstream fragment and a series of deletion mutants were measured in transiently transfected human and mouse macrophage THP-1 and Raw264.7 cells, respectively. A fragment 471 bp upstream of the EMMPRIN coding region was sufficient to promote transcription, while a region from -1413 to -1024 bp suppressed activity. Further deletion analysis of the 471 bp fragment indicated that a 30 bp element from -142 to -112 bp, which contains binding sites for Sp1, AP1TFII and EGR-2, was important for EMMPRIN transcription in both THP-1 and Raw264.7 macrophages. Using electrophoretic mobility shift assays, the Sp1 element within 30 bp region specifically bound Sp1 and Sp3 transcription factors. Mutation of the Sp1 element at -122 to -116 bp of the EMMPRIN promoter significantly diminished promoter activity and formation of DNA-nuclear protein complex. Transient expression of Sp1 and/or Sp3 transcription factors in insect cells lacking the Sp family of transcription factors, stimulated EMMPRIN promoter activity in a synergistic manner. Together, these results indicate that both Sp1 and Sp3 associate with the functional Sp1 element on the EMMPRIN promoter and cooperate in the regulation of EMMPRIN gene expression in macrophages.
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PMID:Characterization of the promoter of human extracellular matrix metalloproteinase inducer (EMMPRIN). 1181 79

From experimental and clinical studies it is known that matrix conservation and degradation by matrix metalloproteinases (MMPs) plays a major role in plaque progression and destabilization with related onset of acute vascular events such as acute coronary syndromes or cerebrovascular accidents. Recently, extracellular MMPs inducer (EMMPRIN) has been reported to induce and activate the expression of MMPs in myocardium and plays an important role in the ventricular remodeling in human heart failure. Similarly to heart failure myocardium, EMMPRIN may be expressed in human atheroma and play a role in the extracellular matrix (ECM) remodeling and atherogenic cell differentiation. This study was designed to investigate the possible biological role of EMMPRIN in human atheroma. Immunohistochemical analysis for MMPs and EMMPRIN was performed on human carotid endarterectomy specimens and control aortas. EMMPRIN showed significant immunoreactivity in human atherosclerotic carotid lesions, and was colocalized with macrophage/monocyte infiltrates in atherosclerotic intima, plaque itself and vascular smooth muscle cells (VSMCs). Zymography and Western blot analysis revealed EMMPRIN expression in the carotid atheromas, but not in the control aortas. Human bone marrow monocytes, which were cultured with atherogenic proinflammatory cytokine stimulation revealed increased EMMPRIN and MMPs expressions. ECM remodeling is under the control of induction and inhibition of matrix degrading protease and the novel MMP inducer, EMMPRIN may play a role in influx and differentiation of monocytes and destabilizing atheroma.
Atherosclerosis 2005 May
PMID:Upstream regulation of matrix metalloproteinase by EMMPRIN; extracellular matrix metalloproteinase inducer in advanced atherosclerotic plaque. 1582 73

Chlamydia (C.) pneumoniae are thought to infect monocytes and use them as vectors into the vessel wall, where they may accelerate atherosclerosis. We investigated the effects of C. pneumoniae on monocytic matrix metalloproteinase (MMP) activation with focus on the role of the extracellular matrix metalloproteinase inducer EMMPRIN. Human monocytes or monocytic MonoMac6 cells were infected with C. pneumoniae. Infection enhanced mRNA- and surface expression of EMMPRIN and Membrane-type-1 Matrix Metalloproteinase (MT1-MMP), plus the secretion of MMP-7, MMP-9 and the urokinase receptor (uPAR). Chlamydial heat shock protein 60 was identified to be partially responsible for EMMPRIN and MMP-9 induction, while C. trachomatis-infection had no stimulatory effect, indicating a C. pneumoniae-specific activation pathway. Suppression of EMMPRIN by gene silencing almost completely hindered the induction of MT1-MMP and MMP-9 by C. pneumoniae, suggesting a predominant regulatory role for EMMPRIN. Moreover, C. pneumoniae-infected monocytes exhibited increased MMP- and plasmin-dependent migration through "matrigel". Additionally, incubation of SMCs with supernatants of C. pneumoniae-infected monocytes induced MMP-2 activation, which was inhibited by IL1-Receptor antagonist or anti-IL-6-mAb, indicating paracrine intercellular activation pathways. In conclusion, C.pneumoniae induce MMP activity directly in monocytes through an EMMPRIN-dependent pathway and indirectly in SMCs via monocyte-derived cytokines.
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PMID:EMMPRIN (CD 147) is a central activator of extracellular matrix degradation by Chlamydia pneumoniae-infected monocytes. Implications for plaque rupture. 1654 74

Monocytes, macrophages, and foam cells expressing CD147 can stimulate the production of several matrix metalloproteinases (MMPs) associated with the development of atherosclerosis. We defined theCD147 expression profile and examined the correlation between foam cell development and MMP-2, -9 expressions. Foam cells were derived from U937-stimulated macrophages using various concentrations of oxidized low-density lipoprotein (ox-LDL). PMA-stimulated U937 cells had a 4- to 5-fold increase in CD147 mRNA compared to undifferentiated monocytes and membrane-associated (mCD147) on foam cells decreased in response to ox-LDL in a dose-dependent manner compared to untreated macrophages.In contrast, ox-LDL treatment increased the levels of soluble CD147 (sCD147) and MMP-2, -9 in a dose-dependent manner. Our data suggested that monocyte differentiation up-regulated CD147 expression and lipid enrichment of foam cells had no effect on CD147 mRNA expression. Lipid loading in macrophages reduced mCD147 expression while increasing the levels of MMP-2, -9 and sCD147 in supernatants.
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PMID:Expression of CD147 on phorbol-12-myristate-13-acetate (PMA)-treated U937 cells differentiating into foam cells. 1938 46

The immunoglobulin superfamily member EMMPRIN (CD147) plays an important role in a number of organ systems, including the cardiovascular system. Here we review the contemporary understanding of EMMPRIN and EMMPRIN-associated sequelae in the course of atherosclerosis. A significant body of data documents the pivotal role of EMMPRIN in the complex processes of atherogenesis, atheroprogression, and acute atherosclerothrombosis, a role that goes beyond that of a mere marker of inflammation.
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PMID:The Extracellular Matrix Metalloproteinase Inducer (EMMPRIN, CD147) - a potential novel target in atherothrombosis prevention? 2366

The Basigin (BSG, also known as CD147/extracellular matrix metalloproteinase inducer) belongs to the immunoglobulin superfamily (IgSF). It is a cellular receptor for cyclophilin A (CypA), and is originally known as tumor cell collagenase stimulatory factor (TCSF), which could abundantly expressed on the surface of tumor cells, haematopoietic, monocytes, epithelial endothelial cells and smooth muscle cells. Accumulating evidence showed that BSG played an important role in stimulating the secretion of matrix metalloproteinases (MMPs), which has been reported to be involved in the development of atherosclerosis. Since atherosclerosis is an important risk factor for atherosclerotic cerebral infarction (ACI), we speculate that BSG genetic polymorphisms may influence formation of atherosclerosis and then development of ACI. This study aimed to detect the potential association of the single nucleotide polymorphisms (SNP, -631 G > T, -318 G > C, 10141 G > A and 10826 G > A) of BSG gene in Hunan Han Chinese population with ACI. We genotyped 199 ACI patients and 188 matched healthy controls for the four BSG SNP by method of matrix-assisted laser desorption/ionization-time-offlight mass spectrometry (MALDI-TOF MS). Our results suggested that all the polymorphisms were observed in the subjects from Changsha area of Hunan Province. However, no significant difference was observed between the distribution of these SNP in cases and controls. Therefore, we speculate that BSG genetic polymorphisms might not be an important factor in the development of ACI in our Chinese Han population.
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PMID:Association of BSG genetic polymorphisms with atherosclerotic cerebral infarction in the Han Chinese population. 2439 13

In coronary arteries, plaque disruption, the major acute clinical manifestations of atherosclerosis, leads to a subsequent cardiac event, such as acute myocardial infarction (AMI) and unstable angina pectoris (UA). Numerous reports have shown that high expression of MMP-9 (matrix metalloproteinase-9), MMP-13 (matrix metalloproteinase-13) and EMMPRIN (extracellular matrix metalloproteinase induce) in monocyte/macrophage results in the plaque progression and destabilization. Curcumin exerts well-known anti-inflammatory and antioxidant effects and probably has a protective role in the atherosclerosis. The purpose of our study was to investigate the molecular mechanisms by which curcumin affects MMP-9, MMP13 and EMMPRIN in PMA (phorbol 12-myristate 13-acetate) induced macrophages. Human monocytic cells (THP-1 cells) were pretreated with curcumin or compound C for 1 h, and then induced by PMA for 48 h. Total RNA and proteins were collected for real-time PCR and Western blot analysis, respectively. In the present study, the exposure to curcumin resulted in attenuated JNK, p38, and ERK activation and decreased expression of MMP-9, MMP-13 and EMMPRIN in PMA induced macrophages. Moreover, we demonstrated that AMPK (AMP-activated protein kinase) and PKC (Protein Kinase C) was activated by PMA during monocyte/macrophage differentiation. Furthermore, curcumin reversed PMA stimulated PKC activation and suppressed the chronic activation of AMPK, which in turn reduced the expression of MMP-9, MMP-13 and EMMPRIN. Therefore, it is suggested that curcumin by inhibiting AMPK-MAPK (mitogen activated protein kinase) and PKC pathway may led to down-regulated EMMPRIN, MMP-9 and MMP-13 expression in PMA-induced THP-1 cells.
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PMID:Curcumin inhibits EMMPRIN and MMP-9 expression through AMPK-MAPK and PKC signaling in PMA induced macrophages. 2524 Oct 44

CD147, a member of the immunoglobulin super family, is a well-known potent inducer of extracellular matrix metalloproteinases. Studies show that CD147 is upregulated in inflammatory diseases. Atherosclerosis is a chronic inflammatory disease of the artery wall. Further understanding of the functions of CD147 in atherosclerosis and atherothrombosis may provide a new strategy for preventing and treating cardiovascular disease. In this review, we discuss how CD147 contributes to atherosclerosis and atherothrombosis.
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PMID:Function of CD147 in atherosclerosis and atherothrombosis. 2560 60

The receptor EMMPRIN is involved in the development and progression of cardiovascular diseases and in the pathogenesis of myocardial infarction. There are several binding partners of EMMPRIN mediating the effects of EMMPRIN in cardiovascular diseases. EMMPRIN interaction with most binding partners leads to disease progression by mediating cytokine or chemokine release, the activation of platelets and monocytes, as well as the formation of monocyte-platelet aggregates (MPAs). EMMPRIN is also involved in atherosclerosis by mediating the infiltration of pro-inflammatory cells. There is also evidence that EMMPRIN controls energy metabolism of cells and that EMMPRIN binding partners modulate intracellular glycosylation and trafficking of EMMPRIN towards the cell membrane. In this review, we systematically discuss these multifaceted roles of EMMPRIN and its interaction partners, such as Cyclophilins, in cardiovascular disease.
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PMID:Extracellular Matrix Metalloproteinase Inducer EMMPRIN (CD147) in Cardiovascular Disease. 2941 44

There is growing evidence that highlighted the potential effects of CD147 in atherosclerosis, but the potential implication of CD147 in diagnosis and treatment of transient ischemic attack (TIA) and acute cerebral infarction (ACI) is still unclear. In this work, we investigated the serum level of CD147 in patients with TIA and ACI, and CD147 expression in atherosclerotic plaque. The result showed significantly increasing serum level of CD147 in patients with TIA and ACI, and increasing amount of CD147 in vulnerable plaque compared with that in migrating plaque. The serum level of CD147 was correlation with risk of stroke after an episode of TIA. These results together suggest a potential involvement of CD147 in the development and progression of TIA and ACI and CD147 as a potential biomarker for stroke prediction.
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PMID:Study of Serum CD147 Level in Patients with Transient Ischemic Attack and CD147 Expression in Atherosclerotic Plaque. 3003 37


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