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Oxidized Low Density Lipoproteins Induce mRNA Expression and Release of Endothelin From Human and Porcine Endothelium
Experiments were designed to examine the effect of oxidized low density lipoproteins (Ox-LDLs) on the expression and the release of endothelin from cultured endothelial cells and intact blood vessels. Ox-LDLs (30–300 μg/ml), but not native low density lipoproteins (200 μg/ml), stimulated the express...
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Published in: | Circulation research 1992-06, Vol.70 (6), p.1191-1197 |
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creator | Boulanger, Chantal M Tanner, Felix C Béa, Marie-Luce Hahn, Alfred W.A Werner, Annick Lüscher, Thomas F |
description | Experiments were designed to examine the effect of oxidized low density lipoproteins (Ox-LDLs) on the expression and the release of endothelin from cultured endothelial cells and intact blood vessels. Ox-LDLs (30–300 μg/ml), but not native low density lipoproteins (200 μg/ml), stimulated the expression of preproendothelin mRNA in porcine and human endothelial cells, leading to a time- and concentration-dependent release of the peptide into the culture medium. The Ox-LDL-stimulated release of endothelin was mimicked by acetylated low density lipoprotein and abolished by downregulation of protein kinase C by phorbol ester. In the intact porcine aorta, Ox-LDLs, but not native low density lipoproteins, also increased the release of peptide in an endothelium- and concentration-dependent manner. The maximal effect was observed at a concentration of 100 μg/ml. Incubation of the intact porcine aorta with the scavenger receptor antagonist dextran sulfate decreased the formation of endothelin evoked by Ox-LDLs. The Ox-LDL-stimulated production of the peptide was further augmented in the presence of thrombin (4 units/ml) and was unaffected by nitric oxide-generating compound 3-morpholinosydnonimine (10 M). These results suggest that Ox-LDL may be an endogenous mediator of the augmented release of endothelin observed in hyperlipidemia and atherosclerosis. The increased production of the peptide could contribute to vasospastic events and may promote vascular smooth muscle proliferation and progression of atherosclerotic vascular disease. |
doi_str_mv | 10.1161/01.res.70.6.1191 |
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Ox-LDLs (30–300 μg/ml), but not native low density lipoproteins (200 μg/ml), stimulated the expression of preproendothelin mRNA in porcine and human endothelial cells, leading to a time- and concentration-dependent release of the peptide into the culture medium. The Ox-LDL-stimulated release of endothelin was mimicked by acetylated low density lipoprotein and abolished by downregulation of protein kinase C by phorbol ester. In the intact porcine aorta, Ox-LDLs, but not native low density lipoproteins, also increased the release of peptide in an endothelium- and concentration-dependent manner. The maximal effect was observed at a concentration of 100 μg/ml. Incubation of the intact porcine aorta with the scavenger receptor antagonist dextran sulfate decreased the formation of endothelin evoked by Ox-LDLs. The Ox-LDL-stimulated production of the peptide was further augmented in the presence of thrombin (4 units/ml) and was unaffected by nitric oxide-generating compound 3-morpholinosydnonimine (10 M). These results suggest that Ox-LDL may be an endogenous mediator of the augmented release of endothelin observed in hyperlipidemia and atherosclerosis. The increased production of the peptide could contribute to vasospastic events and may promote vascular smooth muscle proliferation and progression of atherosclerotic vascular disease.</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/01.res.70.6.1191</identifier><identifier>PMID: 1315634</identifier><identifier>CODEN: CIRUAL</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Acetylation ; Animals ; Aorta ; Biological and medical sciences ; Blood vessels and receptors ; Blotting, Northern ; Cells, Cultured ; Cyclic GMP - analysis ; Densitometry ; Endothelins - genetics ; Endothelins - immunology ; Endothelins - metabolism ; Endothelium, Vascular - cytology ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - physiology ; Fundamental and applied biological sciences. Psychology ; Lipoproteins, LDL - pharmacology ; Microscopy, Electron, Scanning ; Oxidation-Reduction ; RNA, Messenger - analysis ; Swine ; Time Factors ; Vertebrates: cardiovascular system</subject><ispartof>Circulation research, 1992-06, Vol.70 (6), p.1191-1197</ispartof><rights>1992 American Heart Association, Inc.</rights><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4754-d20fe00d8ffde7ca1228ea011b821ed657d671e38efb6b3aab6d677c49d892fc3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4354229$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1315634$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Boulanger, Chantal M</creatorcontrib><creatorcontrib>Tanner, Felix C</creatorcontrib><creatorcontrib>Béa, Marie-Luce</creatorcontrib><creatorcontrib>Hahn, Alfred W.A</creatorcontrib><creatorcontrib>Werner, Annick</creatorcontrib><creatorcontrib>Lüscher, Thomas F</creatorcontrib><title>Oxidized Low Density Lipoproteins Induce mRNA Expression and Release of Endothelin From Human and Porcine Endothelium</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>Experiments were designed to examine the effect of oxidized low density lipoproteins (Ox-LDLs) on the expression and the release of endothelin from cultured endothelial cells and intact blood vessels. Ox-LDLs (30–300 μg/ml), but not native low density lipoproteins (200 μg/ml), stimulated the expression of preproendothelin mRNA in porcine and human endothelial cells, leading to a time- and concentration-dependent release of the peptide into the culture medium. The Ox-LDL-stimulated release of endothelin was mimicked by acetylated low density lipoprotein and abolished by downregulation of protein kinase C by phorbol ester. In the intact porcine aorta, Ox-LDLs, but not native low density lipoproteins, also increased the release of peptide in an endothelium- and concentration-dependent manner. The maximal effect was observed at a concentration of 100 μg/ml. Incubation of the intact porcine aorta with the scavenger receptor antagonist dextran sulfate decreased the formation of endothelin evoked by Ox-LDLs. The Ox-LDL-stimulated production of the peptide was further augmented in the presence of thrombin (4 units/ml) and was unaffected by nitric oxide-generating compound 3-morpholinosydnonimine (10 M). These results suggest that Ox-LDL may be an endogenous mediator of the augmented release of endothelin observed in hyperlipidemia and atherosclerosis. The increased production of the peptide could contribute to vasospastic events and may promote vascular smooth muscle proliferation and progression of atherosclerotic vascular disease.</description><subject>Acetylation</subject><subject>Animals</subject><subject>Aorta</subject><subject>Biological and medical sciences</subject><subject>Blood vessels and receptors</subject><subject>Blotting, Northern</subject><subject>Cells, Cultured</subject><subject>Cyclic GMP - analysis</subject><subject>Densitometry</subject><subject>Endothelins - genetics</subject><subject>Endothelins - immunology</subject><subject>Endothelins - metabolism</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Lipoproteins, LDL - pharmacology</subject><subject>Microscopy, Electron, Scanning</subject><subject>Oxidation-Reduction</subject><subject>RNA, Messenger - analysis</subject><subject>Swine</subject><subject>Time Factors</subject><subject>Vertebrates: cardiovascular system</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><recordid>eNpFkU1v1DAQhi0EKtvCnQuSD4hblvFH4uRYlS2ttKJogbPl2BOtIYkXO9G2_HrcZkVPo5n3mRnNO4S8Y7BmrGKfgK0jprWCdZULDXtBVqzkspClYi_JCgCaQgkBr8l5Sr8AmBS8OSNnTLCyEnJF5rt77_xfdHQbjvQzjslPD3TrD-EQw4R-TPR2dLNFOuy-XtLN_SHvSz6M1IyO7rBHk5CGjm5GF6Y99n6k1zEM9GYezAJ9C9H6EZ-JeXhDXnWmT_j2FC_Iz-vNj6ubYnv35fbqcltYqUpZOA4dAri66xwqaxjnNRpgrK05Q1eVylWKoaixa6tWGNNWuaCsbFzd8M6KC_JxmZuP-TNjmvTgk8W-NyOGOWnFG86llBmEBbQxpBSx04foBxMfNAP96LQGpneb71qBrvSj07nl_Wn23A7onhsWa7P-4aSbZE3fRTNan_5jUpSS8yZjcsGOoZ8wpt_9fMSo92j6aa_zA0EA4wVrGg5Vzgp4-uI_j-iXWA</recordid><startdate>199206</startdate><enddate>199206</enddate><creator>Boulanger, Chantal M</creator><creator>Tanner, Felix C</creator><creator>Béa, Marie-Luce</creator><creator>Hahn, Alfred W.A</creator><creator>Werner, Annick</creator><creator>Lüscher, Thomas F</creator><general>American Heart Association, Inc</general><general>Lippincott</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>199206</creationdate><title>Oxidized Low Density Lipoproteins Induce mRNA Expression and Release of Endothelin From Human and Porcine Endothelium</title><author>Boulanger, Chantal M ; Tanner, Felix C ; Béa, Marie-Luce ; Hahn, Alfred W.A ; Werner, Annick ; Lüscher, Thomas F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4754-d20fe00d8ffde7ca1228ea011b821ed657d671e38efb6b3aab6d677c49d892fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Acetylation</topic><topic>Animals</topic><topic>Aorta</topic><topic>Biological and medical sciences</topic><topic>Blood vessels and receptors</topic><topic>Blotting, Northern</topic><topic>Cells, Cultured</topic><topic>Cyclic GMP - analysis</topic><topic>Densitometry</topic><topic>Endothelins - genetics</topic><topic>Endothelins - immunology</topic><topic>Endothelins - metabolism</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Lipoproteins, LDL - pharmacology</topic><topic>Microscopy, Electron, Scanning</topic><topic>Oxidation-Reduction</topic><topic>RNA, Messenger - analysis</topic><topic>Swine</topic><topic>Time Factors</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Boulanger, Chantal M</creatorcontrib><creatorcontrib>Tanner, Felix C</creatorcontrib><creatorcontrib>Béa, Marie-Luce</creatorcontrib><creatorcontrib>Hahn, Alfred W.A</creatorcontrib><creatorcontrib>Werner, Annick</creatorcontrib><creatorcontrib>Lüscher, Thomas F</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>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Boulanger, Chantal M</au><au>Tanner, Felix C</au><au>Béa, Marie-Luce</au><au>Hahn, Alfred W.A</au><au>Werner, Annick</au><au>Lüscher, Thomas F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oxidized Low Density Lipoproteins Induce mRNA Expression and Release of Endothelin From Human and Porcine Endothelium</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>1992-06</date><risdate>1992</risdate><volume>70</volume><issue>6</issue><spage>1191</spage><epage>1197</epage><pages>1191-1197</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><coden>CIRUAL</coden><abstract>Experiments were designed to examine the effect of oxidized low density lipoproteins (Ox-LDLs) on the expression and the release of endothelin from cultured endothelial cells and intact blood vessels. Ox-LDLs (30–300 μg/ml), but not native low density lipoproteins (200 μg/ml), stimulated the expression of preproendothelin mRNA in porcine and human endothelial cells, leading to a time- and concentration-dependent release of the peptide into the culture medium. The Ox-LDL-stimulated release of endothelin was mimicked by acetylated low density lipoprotein and abolished by downregulation of protein kinase C by phorbol ester. In the intact porcine aorta, Ox-LDLs, but not native low density lipoproteins, also increased the release of peptide in an endothelium- and concentration-dependent manner. The maximal effect was observed at a concentration of 100 μg/ml. Incubation of the intact porcine aorta with the scavenger receptor antagonist dextran sulfate decreased the formation of endothelin evoked by Ox-LDLs. The Ox-LDL-stimulated production of the peptide was further augmented in the presence of thrombin (4 units/ml) and was unaffected by nitric oxide-generating compound 3-morpholinosydnonimine (10 M). These results suggest that Ox-LDL may be an endogenous mediator of the augmented release of endothelin observed in hyperlipidemia and atherosclerosis. The increased production of the peptide could contribute to vasospastic events and may promote vascular smooth muscle proliferation and progression of atherosclerotic vascular disease.</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>1315634</pmid><doi>10.1161/01.res.70.6.1191</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Acetylation Animals Aorta Biological and medical sciences Blood vessels and receptors Blotting, Northern Cells, Cultured Cyclic GMP - analysis Densitometry Endothelins - genetics Endothelins - immunology Endothelins - metabolism Endothelium, Vascular - cytology Endothelium, Vascular - drug effects Endothelium, Vascular - physiology Fundamental and applied biological sciences. Psychology Lipoproteins, LDL - pharmacology Microscopy, Electron, Scanning Oxidation-Reduction RNA, Messenger - analysis Swine Time Factors Vertebrates: cardiovascular system |
title | Oxidized Low Density Lipoproteins Induce mRNA Expression and Release of Endothelin From Human and Porcine Endothelium |
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