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Metabolomic identification of novel biomarkers of myocardial ischemia
Recognition of myocardial ischemia is critical both for the diagnosis of coronary artery disease and the selection and evaluation of therapy. Recent advances in proteomic and metabolic profiling technologies may offer the possibility of identifying novel biomarkers and pathways activated in myocardi...
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| Published in: | Circulation (New York, N.Y.) N.Y.), 2005-12, Vol.112 (25), p.3868-3875 |
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| Main Authors: | , , , , , , , , |
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| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c561t-4f2d67d45eef56e5d93d1bc7a9d8db461a62c88506d97f9f90b4faef385f94373 |
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| cites | cdi_FETCH-LOGICAL-c561t-4f2d67d45eef56e5d93d1bc7a9d8db461a62c88506d97f9f90b4faef385f94373 |
| container_end_page | 3875 |
| container_issue | 25 |
| container_start_page | 3868 |
| container_title | Circulation (New York, N.Y.) |
| container_volume | 112 |
| creator | SABATINE, Marc S LIU, Emerson MORROW, David A HELLER, Eric MCCARROLL, Robert WIEGAND, Roger BERRIZ, Gabriel F ROTH, Frederick P GERSZTEN, Robert E |
| description | Recognition of myocardial ischemia is critical both for the diagnosis of coronary artery disease and the selection and evaluation of therapy. Recent advances in proteomic and metabolic profiling technologies may offer the possibility of identifying novel biomarkers and pathways activated in myocardial ischemia.
Blood samples were obtained before and after exercise stress testing from 36 patients, 18 of whom demonstrated inducible ischemia (cases) and 18 of whom did not (controls). Plasma was fractionated by liquid chromatography, and profiling of analytes was performed with a high-sensitivity electrospray triple-quadrupole mass spectrometer under selected reaction monitoring conditions. Lactic acid and metabolites involved in skeletal muscle AMP catabolism increased after exercise in both cases and controls. In contrast, there was significant discordant regulation of multiple metabolites that either increased or decreased in cases but remained unchanged in controls. Functional pathway trend analysis with the use of novel software revealed that 6 members of the citric acid pathway were among the 23 most changed metabolites in cases (adjusted P=0.04). Furthermore, changes in 6 metabolites, including citric acid, differentiated cases from controls with a high degree of accuracy (P |
| doi_str_mv | 10.1161/circulationaha.105.569137 |
| format | article |
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Blood samples were obtained before and after exercise stress testing from 36 patients, 18 of whom demonstrated inducible ischemia (cases) and 18 of whom did not (controls). Plasma was fractionated by liquid chromatography, and profiling of analytes was performed with a high-sensitivity electrospray triple-quadrupole mass spectrometer under selected reaction monitoring conditions. Lactic acid and metabolites involved in skeletal muscle AMP catabolism increased after exercise in both cases and controls. In contrast, there was significant discordant regulation of multiple metabolites that either increased or decreased in cases but remained unchanged in controls. Functional pathway trend analysis with the use of novel software revealed that 6 members of the citric acid pathway were among the 23 most changed metabolites in cases (adjusted P=0.04). Furthermore, changes in 6 metabolites, including citric acid, differentiated cases from controls with a high degree of accuracy (P<0.0001; cross-validated c-statistic=0.83).
We report the novel application of metabolomics to acute myocardial ischemia, in which we identified novel biomarkers of ischemia, and from pathway trend analysis, coordinate changes in groups of functionally related metabolites.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/circulationaha.105.569137</identifier><identifier>PMID: 16344383</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adenosine Monophosphate - metabolism ; Aged ; Biological and medical sciences ; Biomarkers - blood ; Biomarkers - metabolism ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cardiovascular system ; Case-Control Studies ; Chromatography, High Pressure Liquid ; Citric Acid - metabolism ; Coronary heart disease ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Exercise Test ; Female ; Heart ; Humans ; Lactic Acid - blood ; Male ; Medical sciences ; Metabolism - physiology ; Middle Aged ; Muscle, Skeletal - metabolism ; Myocardial Ischemia - diagnosis ; Pharmacology. Drug treatments ; Risk ; Spectrometry, Mass, Electrospray Ionization ; Vasodilator agents. Cerebral vasodilators</subject><ispartof>Circulation (New York, N.Y.), 2005-12, Vol.112 (25), p.3868-3875</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c561t-4f2d67d45eef56e5d93d1bc7a9d8db461a62c88506d97f9f90b4faef385f94373</citedby><cites>FETCH-LOGICAL-c561t-4f2d67d45eef56e5d93d1bc7a9d8db461a62c88506d97f9f90b4faef385f94373</cites></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=17378789$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16344383$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SABATINE, Marc S</creatorcontrib><creatorcontrib>LIU, Emerson</creatorcontrib><creatorcontrib>MORROW, David A</creatorcontrib><creatorcontrib>HELLER, Eric</creatorcontrib><creatorcontrib>MCCARROLL, Robert</creatorcontrib><creatorcontrib>WIEGAND, Roger</creatorcontrib><creatorcontrib>BERRIZ, Gabriel F</creatorcontrib><creatorcontrib>ROTH, Frederick P</creatorcontrib><creatorcontrib>GERSZTEN, Robert E</creatorcontrib><title>Metabolomic identification of novel biomarkers of myocardial ischemia</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Recognition of myocardial ischemia is critical both for the diagnosis of coronary artery disease and the selection and evaluation of therapy. Recent advances in proteomic and metabolic profiling technologies may offer the possibility of identifying novel biomarkers and pathways activated in myocardial ischemia.
Blood samples were obtained before and after exercise stress testing from 36 patients, 18 of whom demonstrated inducible ischemia (cases) and 18 of whom did not (controls). Plasma was fractionated by liquid chromatography, and profiling of analytes was performed with a high-sensitivity electrospray triple-quadrupole mass spectrometer under selected reaction monitoring conditions. Lactic acid and metabolites involved in skeletal muscle AMP catabolism increased after exercise in both cases and controls. In contrast, there was significant discordant regulation of multiple metabolites that either increased or decreased in cases but remained unchanged in controls. Functional pathway trend analysis with the use of novel software revealed that 6 members of the citric acid pathway were among the 23 most changed metabolites in cases (adjusted P=0.04). Furthermore, changes in 6 metabolites, including citric acid, differentiated cases from controls with a high degree of accuracy (P<0.0001; cross-validated c-statistic=0.83).
We report the novel application of metabolomics to acute myocardial ischemia, in which we identified novel biomarkers of ischemia, and from pathway trend analysis, coordinate changes in groups of functionally related metabolites.</description><subject>Adenosine Monophosphate - metabolism</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - metabolism</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular system</subject><subject>Case-Control Studies</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Citric Acid - metabolism</subject><subject>Coronary heart disease</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Exercise Test</subject><subject>Female</subject><subject>Heart</subject><subject>Humans</subject><subject>Lactic Acid - blood</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolism - physiology</subject><subject>Middle Aged</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Myocardial Ischemia - diagnosis</subject><subject>Pharmacology. Drug treatments</subject><subject>Risk</subject><subject>Spectrometry, Mass, Electrospray Ionization</subject><subject>Vasodilator agents. Cerebral vasodilators</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNpFkMtOwzAQRS0EoqXwCygsYJdix694WVWFVipUQu06cvxQDUkMdoLUvyelkboazejcOzMXgAcEpwgx9KxcUF0lW-cbuZdTBOmUMoEwvwBjRDOSEorFJRhDCEXKcZaNwE2Mn33LMKfXYIQYJgTneAwWb6aVpa987VTitGlaZ536t068TRr_a6qkdL6W4cuEeJzVB69k0E5WiYtqb2onb8GVlVU0d0OdgN3LYjtfpuvN62o-W6eKMtSmxGaacU2oMZYyQ7XAGpWKS6FzXRKGJMtUnlPItOBWWAFLYqWxOKdWEMzxBDydfL-D_-lMbIu6P8FUlWyM72LBcoEgZqgHxQlUwccYjC2-g-t_OBQIFscMi_nqY75bz7arzftsOevHtDhl2GvvhyVdWRt9Vg6h9cDjAMioZGWDbJSLZ45jnvNc4D-hO35v</recordid><startdate>20051220</startdate><enddate>20051220</enddate><creator>SABATINE, Marc S</creator><creator>LIU, Emerson</creator><creator>MORROW, David A</creator><creator>HELLER, Eric</creator><creator>MCCARROLL, Robert</creator><creator>WIEGAND, Roger</creator><creator>BERRIZ, Gabriel F</creator><creator>ROTH, Frederick P</creator><creator>GERSZTEN, Robert E</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></search><sort><creationdate>20051220</creationdate><title>Metabolomic identification of novel biomarkers of myocardial ischemia</title><author>SABATINE, Marc S ; LIU, Emerson ; MORROW, David A ; HELLER, Eric ; MCCARROLL, Robert ; WIEGAND, Roger ; BERRIZ, Gabriel F ; ROTH, Frederick P ; GERSZTEN, Robert E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c561t-4f2d67d45eef56e5d93d1bc7a9d8db461a62c88506d97f9f90b4faef385f94373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adenosine Monophosphate - metabolism</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Biomarkers - metabolism</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cardiovascular system</topic><topic>Case-Control Studies</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Citric Acid - metabolism</topic><topic>Coronary heart disease</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Exercise Test</topic><topic>Female</topic><topic>Heart</topic><topic>Humans</topic><topic>Lactic Acid - blood</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolism - physiology</topic><topic>Middle Aged</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Myocardial Ischemia - diagnosis</topic><topic>Pharmacology. Drug treatments</topic><topic>Risk</topic><topic>Spectrometry, Mass, Electrospray Ionization</topic><topic>Vasodilator agents. Cerebral vasodilators</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SABATINE, Marc S</creatorcontrib><creatorcontrib>LIU, Emerson</creatorcontrib><creatorcontrib>MORROW, David A</creatorcontrib><creatorcontrib>HELLER, Eric</creatorcontrib><creatorcontrib>MCCARROLL, Robert</creatorcontrib><creatorcontrib>WIEGAND, Roger</creatorcontrib><creatorcontrib>BERRIZ, Gabriel F</creatorcontrib><creatorcontrib>ROTH, Frederick P</creatorcontrib><creatorcontrib>GERSZTEN, Robert E</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 (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SABATINE, Marc S</au><au>LIU, Emerson</au><au>MORROW, David A</au><au>HELLER, Eric</au><au>MCCARROLL, Robert</au><au>WIEGAND, Roger</au><au>BERRIZ, Gabriel F</au><au>ROTH, Frederick P</au><au>GERSZTEN, Robert E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolomic identification of novel biomarkers of myocardial ischemia</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2005-12-20</date><risdate>2005</risdate><volume>112</volume><issue>25</issue><spage>3868</spage><epage>3875</epage><pages>3868-3875</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Recognition of myocardial ischemia is critical both for the diagnosis of coronary artery disease and the selection and evaluation of therapy. Recent advances in proteomic and metabolic profiling technologies may offer the possibility of identifying novel biomarkers and pathways activated in myocardial ischemia.
Blood samples were obtained before and after exercise stress testing from 36 patients, 18 of whom demonstrated inducible ischemia (cases) and 18 of whom did not (controls). Plasma was fractionated by liquid chromatography, and profiling of analytes was performed with a high-sensitivity electrospray triple-quadrupole mass spectrometer under selected reaction monitoring conditions. Lactic acid and metabolites involved in skeletal muscle AMP catabolism increased after exercise in both cases and controls. In contrast, there was significant discordant regulation of multiple metabolites that either increased or decreased in cases but remained unchanged in controls. Functional pathway trend analysis with the use of novel software revealed that 6 members of the citric acid pathway were among the 23 most changed metabolites in cases (adjusted P=0.04). Furthermore, changes in 6 metabolites, including citric acid, differentiated cases from controls with a high degree of accuracy (P<0.0001; cross-validated c-statistic=0.83).
We report the novel application of metabolomics to acute myocardial ischemia, in which we identified novel biomarkers of ischemia, and from pathway trend analysis, coordinate changes in groups of functionally related metabolites.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>16344383</pmid><doi>10.1161/circulationaha.105.569137</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 2005-12, Vol.112 (25), p.3868-3875 |
| issn | 0009-7322 1524-4539 |
| language | eng |
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| source | Free E-Journal (出版社公開部分のみ） |
| subjects | Adenosine Monophosphate - metabolism Aged Biological and medical sciences Biomarkers - blood Biomarkers - metabolism Blood and lymphatic vessels Cardiology. Vascular system Cardiovascular system Case-Control Studies Chromatography, High Pressure Liquid Citric Acid - metabolism Coronary heart disease Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Exercise Test Female Heart Humans Lactic Acid - blood Male Medical sciences Metabolism - physiology Middle Aged Muscle, Skeletal - metabolism Myocardial Ischemia - diagnosis Pharmacology. Drug treatments Risk Spectrometry, Mass, Electrospray Ionization Vasodilator agents. Cerebral vasodilators |
| title | Metabolomic identification of novel biomarkers of myocardial ischemia |
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