A novel endothelial-derived lipase that modulates HDL metabolism
High-density lipoprotein (HDL) cholesterol levels are inversely associated with risk of atherosclerotic cardiovascular disease 1 . At least 50% of the variation in HDL cholesterol levels is genetically determined 2 , 3 , but the genes responsible for variation in HDL levels have not been fully eluci...
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| Veröffentlicht in: | Nature genetics 1999-04, Vol.21 (4), p.424-428 |
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| creator | Rader, Daniel J Jaye, Michael Lynch, Kevin J Krawiec, John Marchadier, Dawn Maugeais, Cyrille Doan, Kim South, Victoria Amin, Dilip Perrone, Mark |
| description | High-density lipoprotein (HDL) cholesterol levels are inversely associated with risk of atherosclerotic cardiovascular disease
1
. At least 50% of the variation in HDL cholesterol levels is genetically determined
2
,
3
, but the genes responsible for variation in HDL levels have not been fully elucidated. Lipoprotein lipase (LPL) and hepatic lipase (HL), two members of the triacylglyerol (TG) lipase family, both influence HDL metabolism
2
,
4
,
5
,
6
and the HL (
LIPC
) locus has been associated with variation in HDL cholesterol levels in humans
7
,
8
. We describe here the cloning and
in vivo
functional analysis of a new member of the TG lipase family. In contrast to other family members, this new lipase is synthesized by endothelial cells
in vitro
and thus has been termed endothelial lipase (encoded by the
LIPG
gene). EL is expressed
in vivo
in organs including liver, lung, kidney and placenta, but not in skeletal muscle. In contrast to LPL and HL, EL has a lid of only 19 residues. EL has substantial phospholipase activity, but less triglyceride lipase activity. Overexpression of EL in mice reduced plasma concentrations of HDL cholesterol and its major protein apolipoprotein A-I. The endothelial expression, enzymatic profile and
in vivo
effects of EL suggest that it may have a role in lipoprotein metabolism and vascular biology. |
| doi_str_mv | 10.1038/7766 |
| format | Article |
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1
. At least 50% of the variation in HDL cholesterol levels is genetically determined
2
,
3
, but the genes responsible for variation in HDL levels have not been fully elucidated. Lipoprotein lipase (LPL) and hepatic lipase (HL), two members of the triacylglyerol (TG) lipase family, both influence HDL metabolism
2
,
4
,
5
,
6
and the HL (
LIPC
) locus has been associated with variation in HDL cholesterol levels in humans
7
,
8
. We describe here the cloning and
in vivo
functional analysis of a new member of the TG lipase family. In contrast to other family members, this new lipase is synthesized by endothelial cells
in vitro
and thus has been termed endothelial lipase (encoded by the
LIPG
gene). EL is expressed
in vivo
in organs including liver, lung, kidney and placenta, but not in skeletal muscle. In contrast to LPL and HL, EL has a lid of only 19 residues. EL has substantial phospholipase activity, but less triglyceride lipase activity. Overexpression of EL in mice reduced plasma concentrations of HDL cholesterol and its major protein apolipoprotein A-I. The endothelial expression, enzymatic profile and
in vivo
effects of EL suggest that it may have a role in lipoprotein metabolism and vascular biology.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/7766</identifier><identifier>PMID: 10192396</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Amino Acid Sequence ; Animal Genetics and Genomics ; Animals ; Anticholesteremic Agents - pharmacology ; Apolipoprotein A-I - genetics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Blotting, Northern ; Cancer Research ; Cells, Cultured ; Cholesterol, HDL - blood ; Cholesterol, HDL - drug effects ; Classical genetics, quantitative genetics, hybrids ; Cloning, Molecular ; COS Cells - enzymology ; Endothelium, Vascular - cytology ; Endothelium, Vascular - enzymology ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Function ; Genetics of eukaryotes. Biological and molecular evolution ; Human ; Human Genetics ; Humans ; letter ; Lipase - genetics ; Lipase - metabolism ; Lipoproteins, HDL - blood ; Lipoproteins, HDL - metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Molecular Sequence Data ; Placenta ; Pregnancy ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; Recombinant Proteins - pharmacology ; Sequence Homology, Amino Acid ; Transfection</subject><ispartof>Nature genetics, 1999-04, Vol.21 (4), p.424-428</ispartof><rights>Nature America Inc. 1999</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-d8db58ae4eebdc28264c1297cfe4b53cb70d627fd78db484e51b2c14fff664ad3</citedby><cites>FETCH-LOGICAL-c386t-d8db58ae4eebdc28264c1297cfe4b53cb70d627fd78db484e51b2c14fff664ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/7766$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/7766$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,2727,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1744003$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10192396$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rader, Daniel J</creatorcontrib><creatorcontrib>Jaye, Michael</creatorcontrib><creatorcontrib>Lynch, Kevin J</creatorcontrib><creatorcontrib>Krawiec, John</creatorcontrib><creatorcontrib>Marchadier, Dawn</creatorcontrib><creatorcontrib>Maugeais, Cyrille</creatorcontrib><creatorcontrib>Doan, Kim</creatorcontrib><creatorcontrib>South, Victoria</creatorcontrib><creatorcontrib>Amin, Dilip</creatorcontrib><creatorcontrib>Perrone, Mark</creatorcontrib><title>A novel endothelial-derived lipase that modulates HDL metabolism</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>High-density lipoprotein (HDL) cholesterol levels are inversely associated with risk of atherosclerotic cardiovascular disease
1
. At least 50% of the variation in HDL cholesterol levels is genetically determined
2
,
3
, but the genes responsible for variation in HDL levels have not been fully elucidated. Lipoprotein lipase (LPL) and hepatic lipase (HL), two members of the triacylglyerol (TG) lipase family, both influence HDL metabolism
2
,
4
,
5
,
6
and the HL (
LIPC
) locus has been associated with variation in HDL cholesterol levels in humans
7
,
8
. We describe here the cloning and
in vivo
functional analysis of a new member of the TG lipase family. In contrast to other family members, this new lipase is synthesized by endothelial cells
in vitro
and thus has been termed endothelial lipase (encoded by the
LIPG
gene). EL is expressed
in vivo
in organs including liver, lung, kidney and placenta, but not in skeletal muscle. In contrast to LPL and HL, EL has a lid of only 19 residues. EL has substantial phospholipase activity, but less triglyceride lipase activity. Overexpression of EL in mice reduced plasma concentrations of HDL cholesterol and its major protein apolipoprotein A-I. The endothelial expression, enzymatic profile and
in vivo
effects of EL suggest that it may have a role in lipoprotein metabolism and vascular biology.</description><subject>Agriculture</subject><subject>Amino Acid Sequence</subject><subject>Animal Genetics and Genomics</subject><subject>Animals</subject><subject>Anticholesteremic Agents - pharmacology</subject><subject>Apolipoprotein A-I - genetics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blotting, Northern</subject><subject>Cancer Research</subject><subject>Cells, Cultured</subject><subject>Cholesterol, HDL - blood</subject><subject>Cholesterol, HDL - drug effects</subject><subject>Classical genetics, quantitative genetics, hybrids</subject><subject>Cloning, Molecular</subject><subject>COS Cells - enzymology</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - enzymology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Function</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Human</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>letter</subject><subject>Lipase - genetics</subject><subject>Lipase - metabolism</subject><subject>Lipoproteins, HDL - blood</subject><subject>Lipoproteins, HDL - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Molecular Sequence Data</subject><subject>Placenta</subject><subject>Pregnancy</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - metabolism</subject><subject>Recombinant Proteins - pharmacology</subject><subject>Sequence Homology, Amino Acid</subject><subject>Transfection</subject><issn>1061-4036</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0EtLxDAUhuEgipcZ_4J0oe6qOUmatDsH7zDgRtclTU61krZj0gr-ezN0cMSNqwTy8AVeQuZAL4Dy_FIpKXfIIWRCpqAg3413KiEVlMsDchTCO6UgBM33yQFQKBgv5CG5WiRd_4kuwc72wxu6RrvUom8-0SauWemAyfCmh6Tt7ej0gCF5uFkmLQ666l0T2jnZq7ULeLw5Z-Tl7vb5-iFdPt0_Xi-WqeG5HFKb2yrLNQrEyhqWMykMsEKZGkWVcVMpaiVTtVURilxgBhUzIOq6llJoy2fkfNpd-f5jxDCUbRMMOqc77MdQykLKApT4F4JiggGHCE8naHwfgse6XPmm1f6rBFquk5brpJGdbPbGqkX7C00NtzsxltGu9rozTdg6FaNTHtnZxEJ86V7Rl-_96LvY7O9_yeQ6PYwef3a6VyqKohRM8G8HZZOn</recordid><startdate>19990401</startdate><enddate>19990401</enddate><creator>Rader, Daniel J</creator><creator>Jaye, Michael</creator><creator>Lynch, Kevin J</creator><creator>Krawiec, John</creator><creator>Marchadier, Dawn</creator><creator>Maugeais, Cyrille</creator><creator>Doan, Kim</creator><creator>South, Victoria</creator><creator>Amin, Dilip</creator><creator>Perrone, Mark</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>19990401</creationdate><title>A novel endothelial-derived lipase that modulates HDL metabolism</title><author>Rader, Daniel J ; Jaye, Michael ; Lynch, Kevin J ; Krawiec, John ; Marchadier, Dawn ; Maugeais, Cyrille ; Doan, Kim ; South, Victoria ; Amin, Dilip ; Perrone, Mark</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-d8db58ae4eebdc28264c1297cfe4b53cb70d627fd78db484e51b2c14fff664ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Agriculture</topic><topic>Amino Acid Sequence</topic><topic>Animal Genetics and Genomics</topic><topic>Animals</topic><topic>Anticholesteremic Agents - pharmacology</topic><topic>Apolipoprotein A-I - genetics</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blotting, Northern</topic><topic>Cancer Research</topic><topic>Cells, Cultured</topic><topic>Cholesterol, HDL - blood</topic><topic>Cholesterol, HDL - drug effects</topic><topic>Classical genetics, quantitative genetics, hybrids</topic><topic>Cloning, Molecular</topic><topic>COS Cells - enzymology</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - enzymology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Function</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Human</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>letter</topic><topic>Lipase - genetics</topic><topic>Lipase - metabolism</topic><topic>Lipoproteins, HDL - blood</topic><topic>Lipoproteins, HDL - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Molecular Sequence Data</topic><topic>Placenta</topic><topic>Pregnancy</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - metabolism</topic><topic>Recombinant Proteins - pharmacology</topic><topic>Sequence Homology, Amino Acid</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rader, Daniel J</creatorcontrib><creatorcontrib>Jaye, Michael</creatorcontrib><creatorcontrib>Lynch, Kevin J</creatorcontrib><creatorcontrib>Krawiec, John</creatorcontrib><creatorcontrib>Marchadier, Dawn</creatorcontrib><creatorcontrib>Maugeais, Cyrille</creatorcontrib><creatorcontrib>Doan, Kim</creatorcontrib><creatorcontrib>South, Victoria</creatorcontrib><creatorcontrib>Amin, Dilip</creatorcontrib><creatorcontrib>Perrone, Mark</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>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rader, Daniel J</au><au>Jaye, Michael</au><au>Lynch, Kevin J</au><au>Krawiec, John</au><au>Marchadier, Dawn</au><au>Maugeais, Cyrille</au><au>Doan, Kim</au><au>South, Victoria</au><au>Amin, Dilip</au><au>Perrone, Mark</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel endothelial-derived lipase that modulates HDL metabolism</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>1999-04-01</date><risdate>1999</risdate><volume>21</volume><issue>4</issue><spage>424</spage><epage>428</epage><pages>424-428</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><coden>NGENEC</coden><abstract>High-density lipoprotein (HDL) cholesterol levels are inversely associated with risk of atherosclerotic cardiovascular disease
1
. At least 50% of the variation in HDL cholesterol levels is genetically determined
2
,
3
, but the genes responsible for variation in HDL levels have not been fully elucidated. Lipoprotein lipase (LPL) and hepatic lipase (HL), two members of the triacylglyerol (TG) lipase family, both influence HDL metabolism
2
,
4
,
5
,
6
and the HL (
LIPC
) locus has been associated with variation in HDL cholesterol levels in humans
7
,
8
. We describe here the cloning and
in vivo
functional analysis of a new member of the TG lipase family. In contrast to other family members, this new lipase is synthesized by endothelial cells
in vitro
and thus has been termed endothelial lipase (encoded by the
LIPG
gene). EL is expressed
in vivo
in organs including liver, lung, kidney and placenta, but not in skeletal muscle. In contrast to LPL and HL, EL has a lid of only 19 residues. EL has substantial phospholipase activity, but less triglyceride lipase activity. Overexpression of EL in mice reduced plasma concentrations of HDL cholesterol and its major protein apolipoprotein A-I. The endothelial expression, enzymatic profile and
in vivo
effects of EL suggest that it may have a role in lipoprotein metabolism and vascular biology.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>10192396</pmid><doi>10.1038/7766</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 1999-04, Vol.21 (4), p.424-428 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69669174 |
| source | MEDLINE; SpringerNature Journals; Nature Journals Online |
| subjects | Agriculture Amino Acid Sequence Animal Genetics and Genomics Animals Anticholesteremic Agents - pharmacology Apolipoprotein A-I - genetics Biological and medical sciences Biomedical and Life Sciences Biomedicine Blotting, Northern Cancer Research Cells, Cultured Cholesterol, HDL - blood Cholesterol, HDL - drug effects Classical genetics, quantitative genetics, hybrids Cloning, Molecular COS Cells - enzymology Endothelium, Vascular - cytology Endothelium, Vascular - enzymology Female Fundamental and applied biological sciences. Psychology Gene Function Genetics of eukaryotes. Biological and molecular evolution Human Human Genetics Humans letter Lipase - genetics Lipase - metabolism Lipoproteins, HDL - blood Lipoproteins, HDL - metabolism Mice Mice, Inbred C57BL Mice, Transgenic Molecular Sequence Data Placenta Pregnancy Recombinant Proteins - genetics Recombinant Proteins - metabolism Recombinant Proteins - pharmacology Sequence Homology, Amino Acid Transfection |
| title | A novel endothelial-derived lipase that modulates HDL metabolism |
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