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Effect of enalapril and losartan on cytokines in patients with stable angina pectoris awaiting coronary artery bypass grafting and their interaction with polymorphisms in the interleukin-6 gene
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may have anti-inflammatory actions, an effect that could explain some of their beneficial effects on cardiovascular events in clinical trials. Coronary artery bypass grafting (CABG) is associated with a systemic inflammatory...
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Published in: | The American journal of cardiology 2004-09, Vol.94 (5), p.564-569 |
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description | Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may have anti-inflammatory actions, an effect that could explain some of their beneficial effects on cardiovascular events in clinical trials. Coronary artery bypass grafting (CABG) is associated with a systemic inflammatory response and provides a convenient model to examine the effects of such agents. Genetic polymorphisms may be important in influencing the expression of cytokines, such as interleukin-6 (IL-6). We randomized men awaiting CABG to treatment with enalapril, losartan, or control for 2 months before surgery. Systemic IL-6, IL-8, IL-10, and IL-1 receptor agonists were measured before and after surgery, and genotypes for the −174 G/C and −572 G/C IL-6 gene polymorphisms were determined. Total release of the IL-1 receptor agonist was decreased 29% by enalapril and 31% by losartan (adjusted p = 0.041). IL-6 was decreased 17% by enalapril and 20% by losartan. Subjects possessing the −174 GG genotype produced 20% more IL-6 (adjusted p = 0.029). In these high producers of IL-6, release of IL-6 was decreased 51% by enalapril (adjusted p = 0.001) and 32% by losartan (adjusted p = 0.068). Release of IL-10 was nonsignificantly decreased 26% by enalapril and 21% by losartan, whereas IL-8 was not detected. In conclusion, enalapril and losartan significantly decreased release of the IL-1 receptor agonist after CABG. Enalapril produced a highly significant decrease of 51% in the release of IL-6 in patients identified as high producers of IL-6 by the −174 G/C polymorphism, whereas losartan has a similar but less marked effect. The production of IL-6 in this setting is influenced by the −174 G/C polymorphism. |
doi_str_mv | 10.1016/j.amjcard.2004.05.017 |
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Coronary artery bypass grafting (CABG) is associated with a systemic inflammatory response and provides a convenient model to examine the effects of such agents. Genetic polymorphisms may be important in influencing the expression of cytokines, such as interleukin-6 (IL-6). We randomized men awaiting CABG to treatment with enalapril, losartan, or control for 2 months before surgery. Systemic IL-6, IL-8, IL-10, and IL-1 receptor agonists were measured before and after surgery, and genotypes for the −174 G/C and −572 G/C IL-6 gene polymorphisms were determined. Total release of the IL-1 receptor agonist was decreased 29% by enalapril and 31% by losartan (adjusted p = 0.041). IL-6 was decreased 17% by enalapril and 20% by losartan. Subjects possessing the −174 GG genotype produced 20% more IL-6 (adjusted p = 0.029). In these high producers of IL-6, release of IL-6 was decreased 51% by enalapril (adjusted p = 0.001) and 32% by losartan (adjusted p = 0.068). Release of IL-10 was nonsignificantly decreased 26% by enalapril and 21% by losartan, whereas IL-8 was not detected. In conclusion, enalapril and losartan significantly decreased release of the IL-1 receptor agonist after CABG. Enalapril produced a highly significant decrease of 51% in the release of IL-6 in patients identified as high producers of IL-6 by the −174 G/C polymorphism, whereas losartan has a similar but less marked effect. The production of IL-6 in this setting is influenced by the −174 G/C polymorphism.</description><identifier>ISSN: 0002-9149</identifier><identifier>EISSN: 1879-1913</identifier><identifier>DOI: 10.1016/j.amjcard.2004.05.017</identifier><identifier>PMID: 15342284</identifier><identifier>CODEN: AJCDAG</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Aged ; Angina pectoris ; Angina Pectoris - drug therapy ; Angina Pectoris - genetics ; Angina Pectoris - immunology ; Angina Pectoris - surgery ; Antihypertensive Agents - pharmacology ; Biological and medical sciences ; Cardiology ; Cardiology. Vascular system ; Coronary Artery Bypass ; Coronary heart disease ; Coronary vessels ; Cytokines ; Cytokines - blood ; Cytokines - drug effects ; Cytokines - genetics ; Enalapril - pharmacology ; Genes ; Genotype ; Heart ; Humans ; Interleukin-6 - genetics ; Losartan - pharmacology ; Male ; Medical sciences ; Middle Aged ; Pharmaceuticals ; Polymorphism ; Polymorphism, Genetic ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the heart</subject><ispartof>The American journal of cardiology, 2004-09, Vol.94 (5), p.564-569</ispartof><rights>2004 Excerpta Medica Inc.</rights><rights>2004 INIST-CNRS</rights><rights>Copyright 2004 Excerpta Medica, Inc.</rights><rights>Copyright Elsevier Sequoia S.A. Sep 1, 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c333t-3b8b3d319cd29737d0aeeb8e63183a1d20b19aa730546ccb01c9d1fb8c8421183</citedby><cites>FETCH-LOGICAL-c333t-3b8b3d319cd29737d0aeeb8e63183a1d20b19aa730546ccb01c9d1fb8c8421183</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=16096388$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15342284$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Trevelyan, Jasper</creatorcontrib><creatorcontrib>Brull, David J.</creatorcontrib><creatorcontrib>Needham, Edward W.A.</creatorcontrib><creatorcontrib>Montgomery, Hugh E.</creatorcontrib><creatorcontrib>Morris, Alan</creatorcontrib><creatorcontrib>Mattu, Raj K.</creatorcontrib><title>Effect of enalapril and losartan on cytokines in patients with stable angina pectoris awaiting coronary artery bypass grafting and their interaction with polymorphisms in the interleukin-6 gene</title><title>The American journal of cardiology</title><addtitle>Am J Cardiol</addtitle><description>Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may have anti-inflammatory actions, an effect that could explain some of their beneficial effects on cardiovascular events in clinical trials. Coronary artery bypass grafting (CABG) is associated with a systemic inflammatory response and provides a convenient model to examine the effects of such agents. Genetic polymorphisms may be important in influencing the expression of cytokines, such as interleukin-6 (IL-6). We randomized men awaiting CABG to treatment with enalapril, losartan, or control for 2 months before surgery. Systemic IL-6, IL-8, IL-10, and IL-1 receptor agonists were measured before and after surgery, and genotypes for the −174 G/C and −572 G/C IL-6 gene polymorphisms were determined. Total release of the IL-1 receptor agonist was decreased 29% by enalapril and 31% by losartan (adjusted p = 0.041). IL-6 was decreased 17% by enalapril and 20% by losartan. Subjects possessing the −174 GG genotype produced 20% more IL-6 (adjusted p = 0.029). In these high producers of IL-6, release of IL-6 was decreased 51% by enalapril (adjusted p = 0.001) and 32% by losartan (adjusted p = 0.068). Release of IL-10 was nonsignificantly decreased 26% by enalapril and 21% by losartan, whereas IL-8 was not detected. In conclusion, enalapril and losartan significantly decreased release of the IL-1 receptor agonist after CABG. Enalapril produced a highly significant decrease of 51% in the release of IL-6 in patients identified as high producers of IL-6 by the −174 G/C polymorphism, whereas losartan has a similar but less marked effect. The production of IL-6 in this setting is influenced by the −174 G/C polymorphism.</description><subject>Aged</subject><subject>Angina pectoris</subject><subject>Angina Pectoris - drug therapy</subject><subject>Angina Pectoris - genetics</subject><subject>Angina Pectoris - immunology</subject><subject>Angina Pectoris - surgery</subject><subject>Antihypertensive Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cardiology</subject><subject>Cardiology. Vascular system</subject><subject>Coronary Artery Bypass</subject><subject>Coronary heart disease</subject><subject>Coronary vessels</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Cytokines - drug effects</subject><subject>Cytokines - genetics</subject><subject>Enalapril - pharmacology</subject><subject>Genes</subject><subject>Genotype</subject><subject>Heart</subject><subject>Humans</subject><subject>Interleukin-6 - genetics</subject><subject>Losartan - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmaceuticals</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the heart</subject><issn>0002-9149</issn><issn>1879-1913</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><recordid>eNqFkV-L1DAUxYMo7jj6EZQg6FvHpGkz7ZPIsqvCgi_6HG7T25mMbVKTzC7z8fxme-cPLPjiUwj53XNuzmHsrRQrKaT-tFvBtLMQ-1UpRLUS9UrI9TO2kM26LWQr1XO2EEKURSur9oq9SmlHVylr_ZJdyVpVZdlUC_b3ZhjQZh4Gjh5GmKMbOfiejyFBzOB58NwecvjtPCbuPJ8hO_Q58QeXtzxl6EakiY3zwGeSCtElDg_gsvMbbkMMHuKBkxjS0R1mSIlvIgyn96NV3qKLJE0A2OzI8CQ9h_EwhThvXZpOzsSdqRH3tE6h-QY9vmYvBhgTvrmcS_br9ubn9bfi7sfX79df7gqrlMqF6ppO9Uq2ti_btVr3AhC7BrWSjQLZl6KTLcBaibrS1nZC2raXQ9fYpiolMUv28aw7x_BnjymbySWL4wgewz4ZrRulhdYEvv8H3IV9pHCTKZUgpqWFlqw-QzaGlCIOhpKfKCgjhTkWbHbmUrA5FmxEbahgmnt3Ed93E_ZPU5dGCfhwASBZGIcI3rr0xJG9Vs3xO5_PHFJm9w6jSZZ6tdi7SC2aPrj_rPIIRcrLTg</recordid><startdate>20040901</startdate><enddate>20040901</enddate><creator>Trevelyan, Jasper</creator><creator>Brull, David J.</creator><creator>Needham, Edward W.A.</creator><creator>Montgomery, Hugh E.</creator><creator>Morris, Alan</creator><creator>Mattu, Raj K.</creator><general>Elsevier Inc</general><general>Elsevier</general><general>Elsevier Limited</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>7TS</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>M7Z</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20040901</creationdate><title>Effect of enalapril and losartan on cytokines in patients with stable angina pectoris awaiting coronary artery bypass grafting and their interaction with polymorphisms in the interleukin-6 gene</title><author>Trevelyan, Jasper ; Brull, David J. ; Needham, Edward W.A. ; Montgomery, Hugh E. ; Morris, Alan ; Mattu, Raj K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c333t-3b8b3d319cd29737d0aeeb8e63183a1d20b19aa730546ccb01c9d1fb8c8421183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Aged</topic><topic>Angina pectoris</topic><topic>Angina Pectoris - drug therapy</topic><topic>Angina Pectoris - genetics</topic><topic>Angina Pectoris - immunology</topic><topic>Angina Pectoris - surgery</topic><topic>Antihypertensive Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cardiology</topic><topic>Cardiology. Vascular system</topic><topic>Coronary Artery Bypass</topic><topic>Coronary heart disease</topic><topic>Coronary vessels</topic><topic>Cytokines</topic><topic>Cytokines - blood</topic><topic>Cytokines - drug effects</topic><topic>Cytokines - genetics</topic><topic>Enalapril - pharmacology</topic><topic>Genes</topic><topic>Genotype</topic><topic>Heart</topic><topic>Humans</topic><topic>Interleukin-6 - genetics</topic><topic>Losartan - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pharmaceuticals</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the heart</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Trevelyan, Jasper</creatorcontrib><creatorcontrib>Brull, David J.</creatorcontrib><creatorcontrib>Needham, Edward W.A.</creatorcontrib><creatorcontrib>Montgomery, Hugh E.</creatorcontrib><creatorcontrib>Morris, Alan</creatorcontrib><creatorcontrib>Mattu, Raj K.</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>Physical Education Index</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biochemistry Abstracts 1</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The American journal of cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Trevelyan, Jasper</au><au>Brull, David J.</au><au>Needham, Edward W.A.</au><au>Montgomery, Hugh E.</au><au>Morris, Alan</au><au>Mattu, Raj K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of enalapril and losartan on cytokines in patients with stable angina pectoris awaiting coronary artery bypass grafting and their interaction with polymorphisms in the interleukin-6 gene</atitle><jtitle>The American journal of cardiology</jtitle><addtitle>Am J Cardiol</addtitle><date>2004-09-01</date><risdate>2004</risdate><volume>94</volume><issue>5</issue><spage>564</spage><epage>569</epage><pages>564-569</pages><issn>0002-9149</issn><eissn>1879-1913</eissn><coden>AJCDAG</coden><abstract>Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may have anti-inflammatory actions, an effect that could explain some of their beneficial effects on cardiovascular events in clinical trials. Coronary artery bypass grafting (CABG) is associated with a systemic inflammatory response and provides a convenient model to examine the effects of such agents. Genetic polymorphisms may be important in influencing the expression of cytokines, such as interleukin-6 (IL-6). We randomized men awaiting CABG to treatment with enalapril, losartan, or control for 2 months before surgery. Systemic IL-6, IL-8, IL-10, and IL-1 receptor agonists were measured before and after surgery, and genotypes for the −174 G/C and −572 G/C IL-6 gene polymorphisms were determined. Total release of the IL-1 receptor agonist was decreased 29% by enalapril and 31% by losartan (adjusted p = 0.041). IL-6 was decreased 17% by enalapril and 20% by losartan. Subjects possessing the −174 GG genotype produced 20% more IL-6 (adjusted p = 0.029). In these high producers of IL-6, release of IL-6 was decreased 51% by enalapril (adjusted p = 0.001) and 32% by losartan (adjusted p = 0.068). Release of IL-10 was nonsignificantly decreased 26% by enalapril and 21% by losartan, whereas IL-8 was not detected. In conclusion, enalapril and losartan significantly decreased release of the IL-1 receptor agonist after CABG. Enalapril produced a highly significant decrease of 51% in the release of IL-6 in patients identified as high producers of IL-6 by the −174 G/C polymorphism, whereas losartan has a similar but less marked effect. The production of IL-6 in this setting is influenced by the −174 G/C polymorphism.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>15342284</pmid><doi>10.1016/j.amjcard.2004.05.017</doi><tpages>6</tpages></addata></record> |
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subjects | Aged Angina pectoris Angina Pectoris - drug therapy Angina Pectoris - genetics Angina Pectoris - immunology Angina Pectoris - surgery Antihypertensive Agents - pharmacology Biological and medical sciences Cardiology Cardiology. Vascular system Coronary Artery Bypass Coronary heart disease Coronary vessels Cytokines Cytokines - blood Cytokines - drug effects Cytokines - genetics Enalapril - pharmacology Genes Genotype Heart Humans Interleukin-6 - genetics Losartan - pharmacology Male Medical sciences Middle Aged Pharmaceuticals Polymorphism Polymorphism, Genetic Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the heart |
title | Effect of enalapril and losartan on cytokines in patients with stable angina pectoris awaiting coronary artery bypass grafting and their interaction with polymorphisms in the interleukin-6 gene |
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