Selective Upregulation of Cardiac Endothelin System in Patients With Ischemic but Not Idiopathic Dilated Cardiomyopathy: Endothelin-1 System in the Human Failing Heart
ABSTRACTOnly scarce information is available on the activity and modifications of the cardiac endothelin (ET)–1 system in heart failure due to ischemic (ICM) or idiopathic dilated (DCM) cardiomyopathy. The activity of the ET-1 system was investigated by measuring cardiac ET-1 and big ET-1 formation...
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| Veröffentlicht in: | Circulation research 2000-03, Vol.86 (4), p.377-385 |
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| creator | Serneri, Gian Gastone Neri Cecioni, Ilaria Vanni, Simone Paniccia, Rita Bandinelli, Brunella Vetere, Annamaria Janming, Xiao Bertolozzi, Iacopo Boddi, Maria Lisi, Gian Franco Sani, Guido Modesti, Pietro Amedeo |
| description | ABSTRACTOnly scarce information is available on the activity and modifications of the cardiac endothelin (ET)–1 system in heart failure due to ischemic (ICM) or idiopathic dilated (DCM) cardiomyopathy. The activity of the ET-1 system was investigated by measuring cardiac ET-1 and big ET-1 formation and quantifying cardiac mRNA for prepro–ET-1 (ppET-1), ET-converting enzyme-1, and ETA and ETB receptors both in myocardium and in isolated myocytes using Northern blot, reverse transcription–polymerase chain reaction, and in situ hybridization in 22 patients with DCM and 20 with ICM who underwent cardiac transplantation and in 7 potential heart transplant donors (nonfailing hearts). Notwithstanding a similar increase of plasma ET-1 in the 2 groups, cardiac ET formation, mRNA levels for ppET-1, and ETA and ETB receptors were higher on both the myocardium and isolated myocytes from ICM than on those from DCM hearts (P |
| doi_str_mv | 10.1161/01.res.86.4.377 |
| format | Article |
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The activity of the ET-1 system was investigated by measuring cardiac ET-1 and big ET-1 formation and quantifying cardiac mRNA for prepro–ET-1 (ppET-1), ET-converting enzyme-1, and ETA and ETB receptors both in myocardium and in isolated myocytes using Northern blot, reverse transcription–polymerase chain reaction, and in situ hybridization in 22 patients with DCM and 20 with ICM who underwent cardiac transplantation and in 7 potential heart transplant donors (nonfailing hearts). Notwithstanding a similar increase of plasma ET-1 in the 2 groups, cardiac ET formation, mRNA levels for ppET-1, and ETA and ETB receptors were higher on both the myocardium and isolated myocytes from ICM than on those from DCM hearts (P <0.001 for all). ppET-1 and ET-converting enzyme-1 mRNAs were expressed on myocytes and endothelial and interstitial cells in ICM, whereas in DCM and nonfailing hearts they were mainly expressed on nonmyocyte cells. In both ICM and DCM, the ETA mRNA signal was expressed on both myocytes and nonmyocyte cells, whereas ETB mRNA was almost exclusively localized on nonmyocyte cells. ETA- and ETB-specific receptor binding was increased on both myocytes and cardiac membranes, showing a positive correlation with left ventricular ejection fraction in ICM (r =0.78 and 0.70) but not in DCM patients. The present results show that human ventricular myocytes express all of the components of the ET-1 system, which is selectively upregulated in ICM patients and appears to be functionally important in the maintenance of cardiac function.</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/01.res.86.4.377</identifier><identifier>PMID: 10700441</identifier><identifier>CODEN: CIRUAL</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Adult ; Aged ; Aspartic Acid Endopeptidases - genetics ; Biological and medical sciences ; Cardiac Output, Low - pathology ; Cardiac Output, Low - physiopathology ; Cardiology. Vascular system ; Cardiomyopathy, Dilated - metabolism ; Cardiomyopathy, Dilated - pathology ; Coronary heart disease ; Endothelin-1 - blood ; Endothelin-1 - physiology ; Endothelin-Converting Enzymes ; Endothelins - biosynthesis ; Endothelins - genetics ; Endothelins - metabolism ; Female ; Heart ; Humans ; Male ; Medical sciences ; Metalloendopeptidases ; Middle Aged ; Myocardial Ischemia - metabolism ; Myocardial Ischemia - pathology ; Myocardium - metabolism ; Myocardium - pathology ; Protein Precursors - biosynthesis ; Protein Precursors - genetics ; Radioligand Assay ; Receptor, Endothelin A ; Receptor, Endothelin B ; Receptors, Endothelin - metabolism ; RNA, Messenger - metabolism ; Up-Regulation</subject><ispartof>Circulation research, 2000-03, Vol.86 (4), p.377-385</ispartof><rights>2000 American Heart Association, Inc.</rights><rights>2000 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Mar 3, 2000</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3847-247e5722169f05a5ed51e2a56982572e98155524474d96d22c02d0a71b7c06713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1306443$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10700441$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Serneri, Gian Gastone Neri</creatorcontrib><creatorcontrib>Cecioni, Ilaria</creatorcontrib><creatorcontrib>Vanni, Simone</creatorcontrib><creatorcontrib>Paniccia, Rita</creatorcontrib><creatorcontrib>Bandinelli, Brunella</creatorcontrib><creatorcontrib>Vetere, Annamaria</creatorcontrib><creatorcontrib>Janming, Xiao</creatorcontrib><creatorcontrib>Bertolozzi, Iacopo</creatorcontrib><creatorcontrib>Boddi, Maria</creatorcontrib><creatorcontrib>Lisi, Gian Franco</creatorcontrib><creatorcontrib>Sani, Guido</creatorcontrib><creatorcontrib>Modesti, Pietro Amedeo</creatorcontrib><title>Selective Upregulation of Cardiac Endothelin System in Patients With Ischemic but Not Idiopathic Dilated Cardiomyopathy: Endothelin-1 System in the Human Failing Heart</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>ABSTRACTOnly scarce information is available on the activity and modifications of the cardiac endothelin (ET)–1 system in heart failure due to ischemic (ICM) or idiopathic dilated (DCM) cardiomyopathy. The activity of the ET-1 system was investigated by measuring cardiac ET-1 and big ET-1 formation and quantifying cardiac mRNA for prepro–ET-1 (ppET-1), ET-converting enzyme-1, and ETA and ETB receptors both in myocardium and in isolated myocytes using Northern blot, reverse transcription–polymerase chain reaction, and in situ hybridization in 22 patients with DCM and 20 with ICM who underwent cardiac transplantation and in 7 potential heart transplant donors (nonfailing hearts). Notwithstanding a similar increase of plasma ET-1 in the 2 groups, cardiac ET formation, mRNA levels for ppET-1, and ETA and ETB receptors were higher on both the myocardium and isolated myocytes from ICM than on those from DCM hearts (P <0.001 for all). ppET-1 and ET-converting enzyme-1 mRNAs were expressed on myocytes and endothelial and interstitial cells in ICM, whereas in DCM and nonfailing hearts they were mainly expressed on nonmyocyte cells. In both ICM and DCM, the ETA mRNA signal was expressed on both myocytes and nonmyocyte cells, whereas ETB mRNA was almost exclusively localized on nonmyocyte cells. ETA- and ETB-specific receptor binding was increased on both myocytes and cardiac membranes, showing a positive correlation with left ventricular ejection fraction in ICM (r =0.78 and 0.70) but not in DCM patients. The present results show that human ventricular myocytes express all of the components of the ET-1 system, which is selectively upregulated in ICM patients and appears to be functionally important in the maintenance of cardiac function.</description><subject>Adult</subject><subject>Aged</subject><subject>Aspartic Acid Endopeptidases - genetics</subject><subject>Biological and medical sciences</subject><subject>Cardiac Output, Low - pathology</subject><subject>Cardiac Output, Low - physiopathology</subject><subject>Cardiology. Vascular system</subject><subject>Cardiomyopathy, Dilated - metabolism</subject><subject>Cardiomyopathy, Dilated - pathology</subject><subject>Coronary heart disease</subject><subject>Endothelin-1 - blood</subject><subject>Endothelin-1 - physiology</subject><subject>Endothelin-Converting Enzymes</subject><subject>Endothelins - biosynthesis</subject><subject>Endothelins - genetics</subject><subject>Endothelins - metabolism</subject><subject>Female</subject><subject>Heart</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metalloendopeptidases</subject><subject>Middle Aged</subject><subject>Myocardial Ischemia - metabolism</subject><subject>Myocardial Ischemia - pathology</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Protein Precursors - biosynthesis</subject><subject>Protein Precursors - genetics</subject><subject>Radioligand Assay</subject><subject>Receptor, Endothelin A</subject><subject>Receptor, Endothelin B</subject><subject>Receptors, Endothelin - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Up-Regulation</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkl9v0zAUxS0EYqPwzBuyEOIt3fWfxAlvU-lopQkQZeLRcpPbxSOJi-0w9RPxNfGWSlQ8-ej456Ore0zIawZzxgp2AWzuMczLYi7nQqkn5JzlXGYyV-wpOQeAKlNCwBl5EcIdAJOCV8_JGQMFICU7J3822GEd7W-kN3uPt2NnonUDdTu6ML6xpqbLoXGxxc4OdHMIEXua1NeE4RAD_WFjS9ehbrG3Nd2OkX52ka4b6_Ymtsn6aFMkNlOc6w-P_uHDSWzGToKTRVdjbwZ6ZWy6vKUrND6-JM92pgv46njOyM3V8vtilV1_-bReXF5ntSilyrhUmCvOWVHtIDc5NjlDbvKiKnnysSpZnqcNSSWbqmg4r4E3YBTbqhoKxcSMvJ9y9979GjFE3dtQY9eZAd0YtIJKgizzBL79D7xzox_SbJozLsXjsmfkYoJq70LwuNN7b3vjD5qBfihQA9PflhtdFlrqVGB68eYYO257bE74qbEEvDsCJtSm23kz1Db84wQUUoqEyQm7d11EH3524z163aLpYqvTxwABjGd8UgKyB6HEX32ysmg</recordid><startdate>20000303</startdate><enddate>20000303</enddate><creator>Serneri, Gian Gastone Neri</creator><creator>Cecioni, Ilaria</creator><creator>Vanni, Simone</creator><creator>Paniccia, Rita</creator><creator>Bandinelli, Brunella</creator><creator>Vetere, Annamaria</creator><creator>Janming, Xiao</creator><creator>Bertolozzi, Iacopo</creator><creator>Boddi, Maria</creator><creator>Lisi, Gian Franco</creator><creator>Sani, Guido</creator><creator>Modesti, Pietro Amedeo</creator><general>American Heart Association, Inc</general><general>Lippincott</general><general>Lippincott Williams & Wilkins Ovid Technologies</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>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20000303</creationdate><title>Selective Upregulation of Cardiac Endothelin System in Patients With Ischemic but Not Idiopathic Dilated Cardiomyopathy: Endothelin-1 System in the Human Failing Heart</title><author>Serneri, Gian Gastone Neri ; Cecioni, Ilaria ; Vanni, Simone ; Paniccia, Rita ; Bandinelli, Brunella ; Vetere, Annamaria ; Janming, Xiao ; Bertolozzi, Iacopo ; Boddi, Maria ; Lisi, Gian Franco ; Sani, Guido ; Modesti, Pietro Amedeo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3847-247e5722169f05a5ed51e2a56982572e98155524474d96d22c02d0a71b7c06713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aspartic Acid Endopeptidases - genetics</topic><topic>Biological and medical sciences</topic><topic>Cardiac Output, Low - pathology</topic><topic>Cardiac Output, Low - physiopathology</topic><topic>Cardiology. Vascular system</topic><topic>Cardiomyopathy, Dilated - metabolism</topic><topic>Cardiomyopathy, Dilated - pathology</topic><topic>Coronary heart disease</topic><topic>Endothelin-1 - blood</topic><topic>Endothelin-1 - physiology</topic><topic>Endothelin-Converting Enzymes</topic><topic>Endothelins - biosynthesis</topic><topic>Endothelins - genetics</topic><topic>Endothelins - metabolism</topic><topic>Female</topic><topic>Heart</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metalloendopeptidases</topic><topic>Middle Aged</topic><topic>Myocardial Ischemia - metabolism</topic><topic>Myocardial Ischemia - pathology</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Protein Precursors - biosynthesis</topic><topic>Protein Precursors - genetics</topic><topic>Radioligand Assay</topic><topic>Receptor, Endothelin A</topic><topic>Receptor, Endothelin B</topic><topic>Receptors, Endothelin - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Serneri, Gian Gastone Neri</creatorcontrib><creatorcontrib>Cecioni, Ilaria</creatorcontrib><creatorcontrib>Vanni, Simone</creatorcontrib><creatorcontrib>Paniccia, Rita</creatorcontrib><creatorcontrib>Bandinelli, Brunella</creatorcontrib><creatorcontrib>Vetere, Annamaria</creatorcontrib><creatorcontrib>Janming, Xiao</creatorcontrib><creatorcontrib>Bertolozzi, Iacopo</creatorcontrib><creatorcontrib>Boddi, Maria</creatorcontrib><creatorcontrib>Lisi, Gian Franco</creatorcontrib><creatorcontrib>Sani, Guido</creatorcontrib><creatorcontrib>Modesti, Pietro Amedeo</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>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Serneri, Gian Gastone Neri</au><au>Cecioni, Ilaria</au><au>Vanni, Simone</au><au>Paniccia, Rita</au><au>Bandinelli, Brunella</au><au>Vetere, Annamaria</au><au>Janming, Xiao</au><au>Bertolozzi, Iacopo</au><au>Boddi, Maria</au><au>Lisi, Gian Franco</au><au>Sani, Guido</au><au>Modesti, Pietro Amedeo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selective Upregulation of Cardiac Endothelin System in Patients With Ischemic but Not Idiopathic Dilated Cardiomyopathy: Endothelin-1 System in the Human Failing Heart</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>2000-03-03</date><risdate>2000</risdate><volume>86</volume><issue>4</issue><spage>377</spage><epage>385</epage><pages>377-385</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><coden>CIRUAL</coden><abstract>ABSTRACTOnly scarce information is available on the activity and modifications of the cardiac endothelin (ET)–1 system in heart failure due to ischemic (ICM) or idiopathic dilated (DCM) cardiomyopathy. The activity of the ET-1 system was investigated by measuring cardiac ET-1 and big ET-1 formation and quantifying cardiac mRNA for prepro–ET-1 (ppET-1), ET-converting enzyme-1, and ETA and ETB receptors both in myocardium and in isolated myocytes using Northern blot, reverse transcription–polymerase chain reaction, and in situ hybridization in 22 patients with DCM and 20 with ICM who underwent cardiac transplantation and in 7 potential heart transplant donors (nonfailing hearts). Notwithstanding a similar increase of plasma ET-1 in the 2 groups, cardiac ET formation, mRNA levels for ppET-1, and ETA and ETB receptors were higher on both the myocardium and isolated myocytes from ICM than on those from DCM hearts (P <0.001 for all). ppET-1 and ET-converting enzyme-1 mRNAs were expressed on myocytes and endothelial and interstitial cells in ICM, whereas in DCM and nonfailing hearts they were mainly expressed on nonmyocyte cells. In both ICM and DCM, the ETA mRNA signal was expressed on both myocytes and nonmyocyte cells, whereas ETB mRNA was almost exclusively localized on nonmyocyte cells. ETA- and ETB-specific receptor binding was increased on both myocytes and cardiac membranes, showing a positive correlation with left ventricular ejection fraction in ICM (r =0.78 and 0.70) but not in DCM patients. The present results show that human ventricular myocytes express all of the components of the ET-1 system, which is selectively upregulated in ICM patients and appears to be functionally important in the maintenance of cardiac function.</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>10700441</pmid><doi>10.1161/01.res.86.4.377</doi><tpages>9</tpages></addata></record> |
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| ispartof | Circulation research, 2000-03, Vol.86 (4), p.377-385 |
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| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Adult Aged Aspartic Acid Endopeptidases - genetics Biological and medical sciences Cardiac Output, Low - pathology Cardiac Output, Low - physiopathology Cardiology. Vascular system Cardiomyopathy, Dilated - metabolism Cardiomyopathy, Dilated - pathology Coronary heart disease Endothelin-1 - blood Endothelin-1 - physiology Endothelin-Converting Enzymes Endothelins - biosynthesis Endothelins - genetics Endothelins - metabolism Female Heart Humans Male Medical sciences Metalloendopeptidases Middle Aged Myocardial Ischemia - metabolism Myocardial Ischemia - pathology Myocardium - metabolism Myocardium - pathology Protein Precursors - biosynthesis Protein Precursors - genetics Radioligand Assay Receptor, Endothelin A Receptor, Endothelin B Receptors, Endothelin - metabolism RNA, Messenger - metabolism Up-Regulation |
| title | Selective Upregulation of Cardiac Endothelin System in Patients With Ischemic but Not Idiopathic Dilated Cardiomyopathy: Endothelin-1 System in the Human Failing Heart |
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