Minimally oxidized low-density lipoprotein regulates hemostasis factors of brain capillary endothelial cells
Minimally oxidized low-density lipoprotein (MM-LDL) is a potent atherogenic lipoprotein. We analyzed the effects of MM-LDL on brain capillary endothelial expression of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and thrombomodulin (TM). Cultured bovine brain c...
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| Veröffentlicht in: | Journal of the neurological sciences 2004-02, Vol.217 (2), p.135-141 |
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| creator | Kim, Jeong Ai Tran, Nam D. Berliner, Judith A. Fisher, Mark J. |
| description | Minimally oxidized low-density lipoprotein (MM-LDL) is a potent atherogenic lipoprotein. We analyzed the effects of MM-LDL on brain capillary endothelial expression of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and thrombomodulin (TM). Cultured bovine brain capillary endothelial cells (BEC) incubated with MM-LDL (25 μg/ml) for 24 h showed increased PAI-1 mRNA levels by approximately seven-fold, while tPA and TM mRNA levels were reduced by 84% and 75%, respectively. Moreover, PAI-1 protein levels increased two-fold (16.8±7.6 vs. 7.6±2.1 ng/ml,
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| doi_str_mv | 10.1016/j.jns.2003.09.006 |
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p<0.05), whereas tPA protein levels decreased by 45% (1.3±0.5 ng/ml vs. 2.3±0.7 ng/ml,
p<0.05), and TM protein level decreased by 40%. Following incubation with MM-LDL, PAI-1 activity was increased 35% (18.4±5.0 vs. 24.8±5.2 AU/ml,
p<0.05), while TM activity was decreased by 30%. MM-LDL therefore has substantial pro-thrombotic effects on brain capillary endothelial cells, reducing both endothelial fibrinolytic capacity (downregulating tPA while upregulating PAI-1) and anticoagulant function (downregulating TM). These results suggest that MM-LDL may contribute to thrombus formation in the brain.</description><identifier>ISSN: 0022-510X</identifier><identifier>EISSN: 1878-5883</identifier><identifier>DOI: 10.1016/j.jns.2003.09.006</identifier><identifier>PMID: 14706215</identifier><identifier>CODEN: JNSCAG</identifier><language>eng</language><publisher>Shannon: Elsevier B.V</publisher><subject>Animals ; Biological and medical sciences ; Blood Coagulation Factors - genetics ; Blood Coagulation Factors - metabolism ; Brain - blood supply ; Cattle ; Cells, Cultured ; Down-Regulation - drug effects ; Down-Regulation - physiology ; Endothelial Cells - metabolism ; Endothelial Cells - pathology ; Endothelium ; Intracranial Thrombosis - etiology ; Intracranial Thrombosis - metabolism ; Intracranial Thrombosis - physiopathology ; Lipoproteins, LDL - metabolism ; Lipoproteins, LDL - pharmacology ; Medical sciences ; Neurology ; Oxidized lipids ; Plasminogen Activator Inhibitor 1 - genetics ; Plasminogen Activator Inhibitor 1 - metabolism ; RNA, Messenger - drug effects ; RNA, Messenger - metabolism ; Thrombomodulin ; Thrombomodulin - genetics ; Thrombomodulin - metabolism ; Tissue plasminogen activator ; Tissue Plasminogen Activator - genetics ; Tissue Plasminogen Activator - metabolism ; Tissue plasminogen activator inhibitor-1 ; Up-Regulation - drug effects ; Up-Regulation - physiology</subject><ispartof>Journal of the neurological sciences, 2004-02, Vol.217 (2), p.135-141</ispartof><rights>2003 Elsevier B.V.</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c379t-f26dd27f817b7bd976cb64ee83f72c10b3a32c24cc1167a7ad6e38adf049d443</citedby><cites>FETCH-LOGICAL-c379t-f26dd27f817b7bd976cb64ee83f72c10b3a32c24cc1167a7ad6e38adf049d443</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jns.2003.09.006$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15389909$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14706215$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Jeong Ai</creatorcontrib><creatorcontrib>Tran, Nam D.</creatorcontrib><creatorcontrib>Berliner, Judith A.</creatorcontrib><creatorcontrib>Fisher, Mark J.</creatorcontrib><title>Minimally oxidized low-density lipoprotein regulates hemostasis factors of brain capillary endothelial cells</title><title>Journal of the neurological sciences</title><addtitle>J Neurol Sci</addtitle><description>Minimally oxidized low-density lipoprotein (MM-LDL) is a potent atherogenic lipoprotein. We analyzed the effects of MM-LDL on brain capillary endothelial expression of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and thrombomodulin (TM). Cultured bovine brain capillary endothelial cells (BEC) incubated with MM-LDL (25 μg/ml) for 24 h showed increased PAI-1 mRNA levels by approximately seven-fold, while tPA and TM mRNA levels were reduced by 84% and 75%, respectively. Moreover, PAI-1 protein levels increased two-fold (16.8±7.6 vs. 7.6±2.1 ng/ml,
p<0.05), whereas tPA protein levels decreased by 45% (1.3±0.5 ng/ml vs. 2.3±0.7 ng/ml,
p<0.05), and TM protein level decreased by 40%. Following incubation with MM-LDL, PAI-1 activity was increased 35% (18.4±5.0 vs. 24.8±5.2 AU/ml,
p<0.05), while TM activity was decreased by 30%. MM-LDL therefore has substantial pro-thrombotic effects on brain capillary endothelial cells, reducing both endothelial fibrinolytic capacity (downregulating tPA while upregulating PAI-1) and anticoagulant function (downregulating TM). These results suggest that MM-LDL may contribute to thrombus formation in the brain.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Coagulation Factors - genetics</subject><subject>Blood Coagulation Factors - metabolism</subject><subject>Brain - blood supply</subject><subject>Cattle</subject><subject>Cells, Cultured</subject><subject>Down-Regulation - drug effects</subject><subject>Down-Regulation - physiology</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelial Cells - pathology</subject><subject>Endothelium</subject><subject>Intracranial Thrombosis - etiology</subject><subject>Intracranial Thrombosis - metabolism</subject><subject>Intracranial Thrombosis - physiopathology</subject><subject>Lipoproteins, LDL - metabolism</subject><subject>Lipoproteins, LDL - pharmacology</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Oxidized lipids</subject><subject>Plasminogen Activator Inhibitor 1 - genetics</subject><subject>Plasminogen Activator Inhibitor 1 - metabolism</subject><subject>RNA, Messenger - drug effects</subject><subject>RNA, Messenger - metabolism</subject><subject>Thrombomodulin</subject><subject>Thrombomodulin - genetics</subject><subject>Thrombomodulin - metabolism</subject><subject>Tissue plasminogen activator</subject><subject>Tissue Plasminogen Activator - genetics</subject><subject>Tissue Plasminogen Activator - metabolism</subject><subject>Tissue plasminogen activator inhibitor-1</subject><subject>Up-Regulation - drug effects</subject><subject>Up-Regulation - physiology</subject><issn>0022-510X</issn><issn>1878-5883</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90D1vFDEQgGELEZEj8ANokBvodjPe3VvbokIRX1IimhR0lteeJT751ofHBzl-PT7dSemopnlmNHoZeyOgFSDG6027WajtAPoWdAswPmMroaRq1kr1z9kKoOuatYAfl-wl0QaqUEq_YJdikDB2Yr1i8S4sYWtjPPD0GHz4i57H9KfxuFAoBx7DLu1yKhgWnvHnPtqCxB9wm6hYCsRn60rKxNPMp2yrcnYXYrT5wHHxqTxgDDZyhzHSK3Yx20j4-jyv2P3nT_c3X5vb71--3Xy8bVwvdWnmbvS-k7MScpKT13J00zggqn6WnRMw9bbvXDc4J8QorbR-xF5ZP8Og_TD0V-z96Wx9_NceqZhtoOMDdsG0J6MA1KCFqFCcoMuJKONsdrnGyAcjwBwLm42phc2xsAFtar-68_Z8fD9t0T9tnJNW8O4MLDkb52wXF-jJrXulNejqPpwc1hK_A2ZDLuDi0IeMrhifwn_e-AfvgJwz</recordid><startdate>20040215</startdate><enddate>20040215</enddate><creator>Kim, Jeong Ai</creator><creator>Tran, Nam D.</creator><creator>Berliner, Judith A.</creator><creator>Fisher, Mark J.</creator><general>Elsevier B.V</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20040215</creationdate><title>Minimally oxidized low-density lipoprotein regulates hemostasis factors of brain capillary endothelial cells</title><author>Kim, Jeong Ai ; Tran, Nam D. ; Berliner, Judith A. ; Fisher, Mark J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c379t-f26dd27f817b7bd976cb64ee83f72c10b3a32c24cc1167a7ad6e38adf049d443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Coagulation Factors - genetics</topic><topic>Blood Coagulation Factors - metabolism</topic><topic>Brain - blood supply</topic><topic>Cattle</topic><topic>Cells, Cultured</topic><topic>Down-Regulation - drug effects</topic><topic>Down-Regulation - physiology</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelial Cells - pathology</topic><topic>Endothelium</topic><topic>Intracranial Thrombosis - etiology</topic><topic>Intracranial Thrombosis - metabolism</topic><topic>Intracranial Thrombosis - physiopathology</topic><topic>Lipoproteins, LDL - metabolism</topic><topic>Lipoproteins, LDL - pharmacology</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>Oxidized lipids</topic><topic>Plasminogen Activator Inhibitor 1 - genetics</topic><topic>Plasminogen Activator Inhibitor 1 - metabolism</topic><topic>RNA, Messenger - drug effects</topic><topic>RNA, Messenger - metabolism</topic><topic>Thrombomodulin</topic><topic>Thrombomodulin - genetics</topic><topic>Thrombomodulin - metabolism</topic><topic>Tissue plasminogen activator</topic><topic>Tissue Plasminogen Activator - genetics</topic><topic>Tissue Plasminogen Activator - metabolism</topic><topic>Tissue plasminogen activator inhibitor-1</topic><topic>Up-Regulation - drug effects</topic><topic>Up-Regulation - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Jeong Ai</creatorcontrib><creatorcontrib>Tran, Nam D.</creatorcontrib><creatorcontrib>Berliner, Judith A.</creatorcontrib><creatorcontrib>Fisher, Mark J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the neurological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Jeong Ai</au><au>Tran, Nam D.</au><au>Berliner, Judith A.</au><au>Fisher, Mark J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Minimally oxidized low-density lipoprotein regulates hemostasis factors of brain capillary endothelial cells</atitle><jtitle>Journal of the neurological sciences</jtitle><addtitle>J Neurol Sci</addtitle><date>2004-02-15</date><risdate>2004</risdate><volume>217</volume><issue>2</issue><spage>135</spage><epage>141</epage><pages>135-141</pages><issn>0022-510X</issn><eissn>1878-5883</eissn><coden>JNSCAG</coden><abstract>Minimally oxidized low-density lipoprotein (MM-LDL) is a potent atherogenic lipoprotein. We analyzed the effects of MM-LDL on brain capillary endothelial expression of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and thrombomodulin (TM). Cultured bovine brain capillary endothelial cells (BEC) incubated with MM-LDL (25 μg/ml) for 24 h showed increased PAI-1 mRNA levels by approximately seven-fold, while tPA and TM mRNA levels were reduced by 84% and 75%, respectively. Moreover, PAI-1 protein levels increased two-fold (16.8±7.6 vs. 7.6±2.1 ng/ml,
p<0.05), whereas tPA protein levels decreased by 45% (1.3±0.5 ng/ml vs. 2.3±0.7 ng/ml,
p<0.05), and TM protein level decreased by 40%. Following incubation with MM-LDL, PAI-1 activity was increased 35% (18.4±5.0 vs. 24.8±5.2 AU/ml,
p<0.05), while TM activity was decreased by 30%. MM-LDL therefore has substantial pro-thrombotic effects on brain capillary endothelial cells, reducing both endothelial fibrinolytic capacity (downregulating tPA while upregulating PAI-1) and anticoagulant function (downregulating TM). These results suggest that MM-LDL may contribute to thrombus formation in the brain.</abstract><cop>Shannon</cop><pub>Elsevier B.V</pub><pmid>14706215</pmid><doi>10.1016/j.jns.2003.09.006</doi><tpages>7</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Blood Coagulation Factors - genetics Blood Coagulation Factors - metabolism Brain - blood supply Cattle Cells, Cultured Down-Regulation - drug effects Down-Regulation - physiology Endothelial Cells - metabolism Endothelial Cells - pathology Endothelium Intracranial Thrombosis - etiology Intracranial Thrombosis - metabolism Intracranial Thrombosis - physiopathology Lipoproteins, LDL - metabolism Lipoproteins, LDL - pharmacology Medical sciences Neurology Oxidized lipids Plasminogen Activator Inhibitor 1 - genetics Plasminogen Activator Inhibitor 1 - metabolism RNA, Messenger - drug effects RNA, Messenger - metabolism Thrombomodulin Thrombomodulin - genetics Thrombomodulin - metabolism Tissue plasminogen activator Tissue Plasminogen Activator - genetics Tissue Plasminogen Activator - metabolism Tissue plasminogen activator inhibitor-1 Up-Regulation - drug effects Up-Regulation - physiology |
| title | Minimally oxidized low-density lipoprotein regulates hemostasis factors of brain capillary endothelial cells |
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