ACAT2 is localized to hepatocytes and is the major cholesterol-esterifying enzyme in human liver
Two acyl-coenzyme A:cholesterol acyltransferase (ACAT) genes, ACAT1 and ACAT2, have been identified that encode 2 proteins responsible for intracellular cholesterol esterification. In this study, immunohistology was used to establish their cellular localization in human liver biopsies. ACAT2 protein...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2004-10, Vol.110 (14), p.2017-2023 |
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| container_title | Circulation (New York, N.Y.) |
| container_volume | 110 |
| creator | PARINI, Paolo DAVIS, Matthew TOMODA, Hiroshi OMURA, Satoshi WILLINGHAM, Mark C RUDEL, Lawrence L LADA, Aaron T ERICKSON, Sandra K WRIGHT, Teresa L GUSTAFSSON, Ulf SAHLIN, Staffan EINARSSON, Curt ERIKSSON, Mats ANGELIN, Bo |
| description | Two acyl-coenzyme A:cholesterol acyltransferase (ACAT) genes, ACAT1 and ACAT2, have been identified that encode 2 proteins responsible for intracellular cholesterol esterification.
In this study, immunohistology was used to establish their cellular localization in human liver biopsies. ACAT2 protein expression was confined to hepatocytes, whereas ACAT1 protein was found in Kupffer cells only. Studies with a highly specific ACAT2 inhibitor, pyripyropene A, in microsomal activity assays demonstrated that ACAT2 activity was highly variable among individual human liver samples, whereas ACAT1 activity was more similar in all specimens. ACAT2 provided the major cholesterol-esterifying activity in 3 of 4 human liver samples examined.
The data suggest that in diseases in which dysregulation of cholesterol metabolism occurs, such as hypercholesterolemia and atherosclerosis, ACAT2 should be considered a target for prevention and treatment. |
| doi_str_mv | 10.1161/01.cir.0000143163.76212.0b |
| format | Article |
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In this study, immunohistology was used to establish their cellular localization in human liver biopsies. ACAT2 protein expression was confined to hepatocytes, whereas ACAT1 protein was found in Kupffer cells only. Studies with a highly specific ACAT2 inhibitor, pyripyropene A, in microsomal activity assays demonstrated that ACAT2 activity was highly variable among individual human liver samples, whereas ACAT1 activity was more similar in all specimens. ACAT2 provided the major cholesterol-esterifying activity in 3 of 4 human liver samples examined.
The data suggest that in diseases in which dysregulation of cholesterol metabolism occurs, such as hypercholesterolemia and atherosclerosis, ACAT2 should be considered a target for prevention and treatment.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.cir.0000143163.76212.0b</identifier><identifier>PMID: 15451793</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adolescent ; Adult ; Aged ; Animals ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood vessels and receptors ; Cardiology. Vascular system ; Cardiovascular system ; Cells, Cultured - enzymology ; Child ; Chlorocebus aethiops ; Cholecystitis - enzymology ; Cholesterol - metabolism ; Cholesterol Esters - biosynthesis ; Dietary Fats - pharmacology ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Enzyme Induction ; Female ; Fundamental and applied biological sciences. Psychology ; Hepatocytes - enzymology ; Humans ; Kupffer Cells - enzymology ; Liver Diseases - enzymology ; Male ; Medical sciences ; Microsomes, Liver - enzymology ; Middle Aged ; Pharmacology. Drug treatments ; Pyridines - pharmacology ; RNA, Messenger - analysis ; Sesquiterpenes - pharmacology ; Species Specificity ; Sterol O-Acyltransferase - analysis ; Sterol O-Acyltransferase - antagonists & inhibitors ; Sterol O-Acyltransferase - biosynthesis ; Sterol O-Acyltransferase - genetics ; Sterol O-Acyltransferase - physiology ; Sterol O-Acyltransferase 2 ; Vasodilator agents. Cerebral vasodilators ; Vertebrates: cardiovascular system</subject><ispartof>Circulation (New York, N.Y.), 2004-10, Vol.110 (14), p.2017-2023</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c603t-24bc09c566307764e1a3a862c443af1fe5d210e90fe11eccdcb27e7bc05f5da73</citedby><cites>FETCH-LOGICAL-c603t-24bc09c566307764e1a3a862c443af1fe5d210e90fe11eccdcb27e7bc05f5da73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3674,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16548774$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15451793$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1959202$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>PARINI, Paolo</creatorcontrib><creatorcontrib>DAVIS, Matthew</creatorcontrib><creatorcontrib>TOMODA, Hiroshi</creatorcontrib><creatorcontrib>OMURA, Satoshi</creatorcontrib><creatorcontrib>WILLINGHAM, Mark C</creatorcontrib><creatorcontrib>RUDEL, Lawrence L</creatorcontrib><creatorcontrib>LADA, Aaron T</creatorcontrib><creatorcontrib>ERICKSON, Sandra K</creatorcontrib><creatorcontrib>WRIGHT, Teresa L</creatorcontrib><creatorcontrib>GUSTAFSSON, Ulf</creatorcontrib><creatorcontrib>SAHLIN, Staffan</creatorcontrib><creatorcontrib>EINARSSON, Curt</creatorcontrib><creatorcontrib>ERIKSSON, Mats</creatorcontrib><creatorcontrib>ANGELIN, Bo</creatorcontrib><title>ACAT2 is localized to hepatocytes and is the major cholesterol-esterifying enzyme in human liver</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Two acyl-coenzyme A:cholesterol acyltransferase (ACAT) genes, ACAT1 and ACAT2, have been identified that encode 2 proteins responsible for intracellular cholesterol esterification.
In this study, immunohistology was used to establish their cellular localization in human liver biopsies. ACAT2 protein expression was confined to hepatocytes, whereas ACAT1 protein was found in Kupffer cells only. Studies with a highly specific ACAT2 inhibitor, pyripyropene A, in microsomal activity assays demonstrated that ACAT2 activity was highly variable among individual human liver samples, whereas ACAT1 activity was more similar in all specimens. ACAT2 provided the major cholesterol-esterifying activity in 3 of 4 human liver samples examined.
The data suggest that in diseases in which dysregulation of cholesterol metabolism occurs, such as hypercholesterolemia and atherosclerosis, ACAT2 should be considered a target for prevention and treatment.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood vessels and receptors</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular system</subject><subject>Cells, Cultured - enzymology</subject><subject>Child</subject><subject>Chlorocebus aethiops</subject><subject>Cholecystitis - enzymology</subject><subject>Cholesterol - metabolism</subject><subject>Cholesterol Esters - biosynthesis</subject><subject>Dietary Fats - pharmacology</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Enzyme Induction</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hepatocytes - enzymology</subject><subject>Humans</subject><subject>Kupffer Cells - enzymology</subject><subject>Liver Diseases - enzymology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microsomes, Liver - enzymology</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyridines - pharmacology</subject><subject>RNA, Messenger - analysis</subject><subject>Sesquiterpenes - pharmacology</subject><subject>Species Specificity</subject><subject>Sterol O-Acyltransferase - analysis</subject><subject>Sterol O-Acyltransferase - antagonists & inhibitors</subject><subject>Sterol O-Acyltransferase - biosynthesis</subject><subject>Sterol O-Acyltransferase - genetics</subject><subject>Sterol O-Acyltransferase - physiology</subject><subject>Sterol O-Acyltransferase 2</subject><subject>Vasodilator agents. Cerebral vasodilators</subject><subject>Vertebrates: cardiovascular system</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkd1O3DAQha2Kqmy3fQVkIcFdUv9707tlVVokpEoVvXYdZ8IaknhrJ1TL02PYqDs3Mx5_Z6zxQeickpJSRb8QWjofS5KDCk4VL7VilJWkfocWVDJRCMmrE7TIQFVoztgp-pjSQz4qruUHdEqlkFRXfIH-rDfrO4Z9wl1wtvPP0OAx4C3s7BjcfoSE7dC83o9bwL19CBG7beggjRBDV7xl3-79cI9heN73gP2At1NvB9z5J4if0PvWdgk-z3mJfl9_u9v8KG5_fr_ZrG8LpwgfCyZqRyonleJEayWAWm5XijkhuG1pC7JhlEBFWqAUnGtczTToLJKtbKzmS1Qc5qZ_sJtqs4u-t3FvgvVmbj3mCoxc8RWrMn954Hcx_J3yGqb3yUHX2QHClIxSFVciw0v09QC6GFKK0P4fTYl59cMQajY3v8zRD_PmhyFXWXw2vzLVPTRH6WxABi5mwKb8_220g_PpyCkpVloL_gLRVZWb</recordid><startdate>20041005</startdate><enddate>20041005</enddate><creator>PARINI, Paolo</creator><creator>DAVIS, Matthew</creator><creator>TOMODA, Hiroshi</creator><creator>OMURA, Satoshi</creator><creator>WILLINGHAM, Mark C</creator><creator>RUDEL, Lawrence L</creator><creator>LADA, Aaron T</creator><creator>ERICKSON, Sandra K</creator><creator>WRIGHT, Teresa L</creator><creator>GUSTAFSSON, Ulf</creator><creator>SAHLIN, Staffan</creator><creator>EINARSSON, Curt</creator><creator>ERIKSSON, Mats</creator><creator>ANGELIN, Bo</creator><general>Lippincott Williams & Wilkins</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><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20041005</creationdate><title>ACAT2 is localized to hepatocytes and is the major cholesterol-esterifying enzyme in human liver</title><author>PARINI, Paolo ; DAVIS, Matthew ; TOMODA, Hiroshi ; OMURA, Satoshi ; WILLINGHAM, Mark C ; RUDEL, Lawrence L ; LADA, Aaron T ; ERICKSON, Sandra K ; WRIGHT, Teresa L ; GUSTAFSSON, Ulf ; SAHLIN, Staffan ; EINARSSON, Curt ; ERIKSSON, Mats ; ANGELIN, Bo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c603t-24bc09c566307764e1a3a862c443af1fe5d210e90fe11eccdcb27e7bc05f5da73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood vessels and receptors</topic><topic>Cardiology. Vascular system</topic><topic>Cardiovascular system</topic><topic>Cells, Cultured - enzymology</topic><topic>Child</topic><topic>Chlorocebus aethiops</topic><topic>Cholecystitis - enzymology</topic><topic>Cholesterol - metabolism</topic><topic>Cholesterol Esters - biosynthesis</topic><topic>Dietary Fats - pharmacology</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Enzyme Induction</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hepatocytes - enzymology</topic><topic>Humans</topic><topic>Kupffer Cells - enzymology</topic><topic>Liver Diseases - enzymology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microsomes, Liver - enzymology</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyridines - pharmacology</topic><topic>RNA, Messenger - analysis</topic><topic>Sesquiterpenes - pharmacology</topic><topic>Species Specificity</topic><topic>Sterol O-Acyltransferase - analysis</topic><topic>Sterol O-Acyltransferase - antagonists & inhibitors</topic><topic>Sterol O-Acyltransferase - biosynthesis</topic><topic>Sterol O-Acyltransferase - genetics</topic><topic>Sterol O-Acyltransferase - physiology</topic><topic>Sterol O-Acyltransferase 2</topic><topic>Vasodilator agents. Cerebral vasodilators</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PARINI, Paolo</creatorcontrib><creatorcontrib>DAVIS, Matthew</creatorcontrib><creatorcontrib>TOMODA, Hiroshi</creatorcontrib><creatorcontrib>OMURA, Satoshi</creatorcontrib><creatorcontrib>WILLINGHAM, Mark C</creatorcontrib><creatorcontrib>RUDEL, Lawrence L</creatorcontrib><creatorcontrib>LADA, Aaron T</creatorcontrib><creatorcontrib>ERICKSON, Sandra K</creatorcontrib><creatorcontrib>WRIGHT, Teresa L</creatorcontrib><creatorcontrib>GUSTAFSSON, Ulf</creatorcontrib><creatorcontrib>SAHLIN, Staffan</creatorcontrib><creatorcontrib>EINARSSON, Curt</creatorcontrib><creatorcontrib>ERIKSSON, Mats</creatorcontrib><creatorcontrib>ANGELIN, Bo</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><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PARINI, Paolo</au><au>DAVIS, Matthew</au><au>TOMODA, Hiroshi</au><au>OMURA, Satoshi</au><au>WILLINGHAM, Mark C</au><au>RUDEL, Lawrence L</au><au>LADA, Aaron T</au><au>ERICKSON, Sandra K</au><au>WRIGHT, Teresa L</au><au>GUSTAFSSON, Ulf</au><au>SAHLIN, Staffan</au><au>EINARSSON, Curt</au><au>ERIKSSON, Mats</au><au>ANGELIN, Bo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ACAT2 is localized to hepatocytes and is the major cholesterol-esterifying enzyme in human liver</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2004-10-05</date><risdate>2004</risdate><volume>110</volume><issue>14</issue><spage>2017</spage><epage>2023</epage><pages>2017-2023</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Two acyl-coenzyme A:cholesterol acyltransferase (ACAT) genes, ACAT1 and ACAT2, have been identified that encode 2 proteins responsible for intracellular cholesterol esterification.
In this study, immunohistology was used to establish their cellular localization in human liver biopsies. ACAT2 protein expression was confined to hepatocytes, whereas ACAT1 protein was found in Kupffer cells only. Studies with a highly specific ACAT2 inhibitor, pyripyropene A, in microsomal activity assays demonstrated that ACAT2 activity was highly variable among individual human liver samples, whereas ACAT1 activity was more similar in all specimens. ACAT2 provided the major cholesterol-esterifying activity in 3 of 4 human liver samples examined.
The data suggest that in diseases in which dysregulation of cholesterol metabolism occurs, such as hypercholesterolemia and atherosclerosis, ACAT2 should be considered a target for prevention and treatment.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>15451793</pmid><doi>10.1161/01.cir.0000143163.76212.0b</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Heart Association Journals; EZB-FREE-00999 freely available EZB journals; Journals@Ovid Complete |
| subjects | Adolescent Adult Aged Animals Biological and medical sciences Blood and lymphatic vessels Blood vessels and receptors Cardiology. Vascular system Cardiovascular system Cells, Cultured - enzymology Child Chlorocebus aethiops Cholecystitis - enzymology Cholesterol - metabolism Cholesterol Esters - biosynthesis Dietary Fats - pharmacology Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Enzyme Induction Female Fundamental and applied biological sciences. Psychology Hepatocytes - enzymology Humans Kupffer Cells - enzymology Liver Diseases - enzymology Male Medical sciences Microsomes, Liver - enzymology Middle Aged Pharmacology. Drug treatments Pyridines - pharmacology RNA, Messenger - analysis Sesquiterpenes - pharmacology Species Specificity Sterol O-Acyltransferase - analysis Sterol O-Acyltransferase - antagonists & inhibitors Sterol O-Acyltransferase - biosynthesis Sterol O-Acyltransferase - genetics Sterol O-Acyltransferase - physiology Sterol O-Acyltransferase 2 Vasodilator agents. Cerebral vasodilators Vertebrates: cardiovascular system |
| title | ACAT2 is localized to hepatocytes and is the major cholesterol-esterifying enzyme in human liver |
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