Upregulation of COX-2 during cardiac allograft rejection
The hypothesis that cyclooxygenase-2 (COX-2) is involved in the myocardial inflammatory response during cardiac allograft rejection was investigated using a rat heterotopic abdominal cardiac transplantation model. COX-2 mRNA and protein in the myocardium of rejecting cardiac allografts were signific...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2000-02, Vol.101 (4), p.430-438 |
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| creator | XIAOCHUN YANG NINSHENG MA GREGORY, S CANNON, P. J SZABOLCS, M. J JING ZHONG ATHAN, E SCIACCA, R. R MICHLER, R. E ANDERSON, G. D WIESE, J. F LEAHY, K. M |
| description | The hypothesis that cyclooxygenase-2 (COX-2) is involved in the myocardial inflammatory response during cardiac allograft rejection was investigated using a rat heterotopic abdominal cardiac transplantation model.
COX-2 mRNA and protein in the myocardium of rejecting cardiac allografts were significantly elevated 3 to 5 days after transplantation compared with syngeneic controls (n=3, P |
| doi_str_mv | 10.1161/01.CIR.101.4.430 |
| format | Article |
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COX-2 mRNA and protein in the myocardium of rejecting cardiac allografts were significantly elevated 3 to 5 days after transplantation compared with syngeneic controls (n=3, P<0.05). COX-2 upregulation paralleled in time and extent the upregulation of iNOS mRNA, protein, and enzyme activity in this model. COX-2 immunostaining was prominent in macrophages infiltrating the rejecting allografts and in damaged cardiac myocytes. Prostaglandin (PG) levels in rejecting allografts were also higher than in native hearts. Because NO has been reported to modulate PG synthesis by COX-2, additional transplants were performed using animals treated with a selective COX-2 inhibitor (SC-58125) and a selective inhibitor of the inducible nitric oxide synthase (iNOS) N-aminomethyl-L-lysine. At posttransplant day 5, inhibitor administration resulted in a significant reduction of COX-2 mRNA expression (3764+/-337 versus 5110+/-141 arbitrary units, n=3, P<0.05) and iNOS enzymatic activity (1.7+/-0.4 versus 22.8+/-14. 4 nmol/mg protein, n=3, P<0.01) compared with vehicle-treated allogeneic transplants. Allograft survival in treated animals was increased modestly from 5.4 to 6.4 days (P<0.05). However, apoptosis of cardiac myocytes (TUNNEL method) was only marginally reduced relative to vehicle controls in treated graft recipients. The intensity of allograft rejection was also similar in the treated and untreated allografts.
The data indicates that COX-2 expression is enhanced in parallel with iNOS in the myocardium during cardiac allograft rejection.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.101.4.430</identifier><identifier>PMID: 10653836</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Biological and medical sciences ; Cyclooxygenase 2 ; Gene Expression Regulation, Enzymologic ; Graft Rejection - enzymology ; Graft Rejection - pathology ; Heart Transplantation - immunology ; Heart Transplantation - pathology ; Isoenzymes - genetics ; Isoenzymes - metabolism ; Male ; Medical sciences ; Nitric Oxide Synthase - genetics ; Nitric Oxide Synthase - metabolism ; Nitric Oxide Synthase Type II ; Prostaglandin-Endoperoxide Synthases - genetics ; Prostaglandin-Endoperoxide Synthases - metabolism ; Protein Biosynthesis ; Rats ; Rats, Inbred Lew ; Rats, Inbred WF ; RNA, Messenger - genetics ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the heart ; Time Factors ; Transcription, Genetic ; Transplantation, Heterotopic ; Transplantation, Homologous ; Transplantation, Isogeneic</subject><ispartof>Circulation (New York, N.Y.), 2000-02, Vol.101 (4), p.430-438</ispartof><rights>2000 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Feb 1, 2000</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-f9c8d80958345b1ceb293fd800b5c31d965eb8813468b5069198db946ebfca753</citedby><cites>FETCH-LOGICAL-c434t-f9c8d80958345b1ceb293fd800b5c31d965eb8813468b5069198db946ebfca753</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3685,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1257848$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10653836$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>XIAOCHUN YANG</creatorcontrib><creatorcontrib>NINSHENG MA</creatorcontrib><creatorcontrib>GREGORY, S</creatorcontrib><creatorcontrib>CANNON, P. J</creatorcontrib><creatorcontrib>SZABOLCS, M. J</creatorcontrib><creatorcontrib>JING ZHONG</creatorcontrib><creatorcontrib>ATHAN, E</creatorcontrib><creatorcontrib>SCIACCA, R. R</creatorcontrib><creatorcontrib>MICHLER, R. E</creatorcontrib><creatorcontrib>ANDERSON, G. D</creatorcontrib><creatorcontrib>WIESE, J. F</creatorcontrib><creatorcontrib>LEAHY, K. M</creatorcontrib><title>Upregulation of COX-2 during cardiac allograft rejection</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>The hypothesis that cyclooxygenase-2 (COX-2) is involved in the myocardial inflammatory response during cardiac allograft rejection was investigated using a rat heterotopic abdominal cardiac transplantation model.
COX-2 mRNA and protein in the myocardium of rejecting cardiac allografts were significantly elevated 3 to 5 days after transplantation compared with syngeneic controls (n=3, P<0.05). COX-2 upregulation paralleled in time and extent the upregulation of iNOS mRNA, protein, and enzyme activity in this model. COX-2 immunostaining was prominent in macrophages infiltrating the rejecting allografts and in damaged cardiac myocytes. Prostaglandin (PG) levels in rejecting allografts were also higher than in native hearts. Because NO has been reported to modulate PG synthesis by COX-2, additional transplants were performed using animals treated with a selective COX-2 inhibitor (SC-58125) and a selective inhibitor of the inducible nitric oxide synthase (iNOS) N-aminomethyl-L-lysine. At posttransplant day 5, inhibitor administration resulted in a significant reduction of COX-2 mRNA expression (3764+/-337 versus 5110+/-141 arbitrary units, n=3, P<0.05) and iNOS enzymatic activity (1.7+/-0.4 versus 22.8+/-14. 4 nmol/mg protein, n=3, P<0.01) compared with vehicle-treated allogeneic transplants. Allograft survival in treated animals was increased modestly from 5.4 to 6.4 days (P<0.05). However, apoptosis of cardiac myocytes (TUNNEL method) was only marginally reduced relative to vehicle controls in treated graft recipients. The intensity of allograft rejection was also similar in the treated and untreated allografts.
The data indicates that COX-2 expression is enhanced in parallel with iNOS in the myocardium during cardiac allograft rejection.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cyclooxygenase 2</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Graft Rejection - enzymology</subject><subject>Graft Rejection - pathology</subject><subject>Heart Transplantation - immunology</subject><subject>Heart Transplantation - pathology</subject><subject>Isoenzymes - genetics</subject><subject>Isoenzymes - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nitric Oxide Synthase - genetics</subject><subject>Nitric Oxide Synthase - metabolism</subject><subject>Nitric Oxide Synthase Type II</subject><subject>Prostaglandin-Endoperoxide Synthases - genetics</subject><subject>Prostaglandin-Endoperoxide Synthases - metabolism</subject><subject>Protein Biosynthesis</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>Rats, Inbred WF</subject><subject>RNA, Messenger - genetics</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the heart</subject><subject>Time Factors</subject><subject>Transcription, Genetic</subject><subject>Transplantation, Heterotopic</subject><subject>Transplantation, Homologous</subject><subject>Transplantation, Isogeneic</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkM9LwzAcxYMobk7vnqSIeGvN7yZHKf4YDAbiwFtI0mR0dO1M2oP_vZkbKJ4e78vnPb48AK4RLBDi6AGiopq_FSgpLSiBJ2CKGKY5ZUSegimEUOYlwXgCLmLcJMtJyc7BBEHOiCB8CsRqF9x6bPXQ9F3W-6xafuQ4q8fQdOvM6lA32ma6bft10H7Igts4u2cvwZnXbXRXR52B1fPTe_WaL5Yv8-pxkVtK6JB7aUUtoGSCUGaQdQZL4tMFGmYJqiVnzgiBCOXCMMglkqI2knJnvNUlIzNwf-jdhf5zdHFQ2yZa17a6c_0YVQlFKiNlAm__gZt-DF36TWGES87gTxs8QDb0MQbn1S40Wx2-FIJqP6mCSKVJk0WKqjRpitwce0ezdfWfwGHDBNwdAR2tbn3QnW3iL4dZKagg35MCe8M</recordid><startdate>20000201</startdate><enddate>20000201</enddate><creator>XIAOCHUN YANG</creator><creator>NINSHENG MA</creator><creator>GREGORY, S</creator><creator>CANNON, P. 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Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the heart</topic><topic>Time Factors</topic><topic>Transcription, Genetic</topic><topic>Transplantation, Heterotopic</topic><topic>Transplantation, Homologous</topic><topic>Transplantation, Isogeneic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>XIAOCHUN YANG</creatorcontrib><creatorcontrib>NINSHENG MA</creatorcontrib><creatorcontrib>GREGORY, S</creatorcontrib><creatorcontrib>CANNON, P. J</creatorcontrib><creatorcontrib>SZABOLCS, M. J</creatorcontrib><creatorcontrib>JING ZHONG</creatorcontrib><creatorcontrib>ATHAN, E</creatorcontrib><creatorcontrib>SCIACCA, R. R</creatorcontrib><creatorcontrib>MICHLER, R. E</creatorcontrib><creatorcontrib>ANDERSON, G. D</creatorcontrib><creatorcontrib>WIESE, J. F</creatorcontrib><creatorcontrib>LEAHY, K. M</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</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>XIAOCHUN YANG</au><au>NINSHENG MA</au><au>GREGORY, S</au><au>CANNON, P. J</au><au>SZABOLCS, M. J</au><au>JING ZHONG</au><au>ATHAN, E</au><au>SCIACCA, R. R</au><au>MICHLER, R. E</au><au>ANDERSON, G. D</au><au>WIESE, J. F</au><au>LEAHY, K. M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Upregulation of COX-2 during cardiac allograft rejection</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2000-02-01</date><risdate>2000</risdate><volume>101</volume><issue>4</issue><spage>430</spage><epage>438</epage><pages>430-438</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>The hypothesis that cyclooxygenase-2 (COX-2) is involved in the myocardial inflammatory response during cardiac allograft rejection was investigated using a rat heterotopic abdominal cardiac transplantation model.
COX-2 mRNA and protein in the myocardium of rejecting cardiac allografts were significantly elevated 3 to 5 days after transplantation compared with syngeneic controls (n=3, P<0.05). COX-2 upregulation paralleled in time and extent the upregulation of iNOS mRNA, protein, and enzyme activity in this model. COX-2 immunostaining was prominent in macrophages infiltrating the rejecting allografts and in damaged cardiac myocytes. Prostaglandin (PG) levels in rejecting allografts were also higher than in native hearts. Because NO has been reported to modulate PG synthesis by COX-2, additional transplants were performed using animals treated with a selective COX-2 inhibitor (SC-58125) and a selective inhibitor of the inducible nitric oxide synthase (iNOS) N-aminomethyl-L-lysine. At posttransplant day 5, inhibitor administration resulted in a significant reduction of COX-2 mRNA expression (3764+/-337 versus 5110+/-141 arbitrary units, n=3, P<0.05) and iNOS enzymatic activity (1.7+/-0.4 versus 22.8+/-14. 4 nmol/mg protein, n=3, P<0.01) compared with vehicle-treated allogeneic transplants. Allograft survival in treated animals was increased modestly from 5.4 to 6.4 days (P<0.05). However, apoptosis of cardiac myocytes (TUNNEL method) was only marginally reduced relative to vehicle controls in treated graft recipients. The intensity of allograft rejection was also similar in the treated and untreated allografts.
The data indicates that COX-2 expression is enhanced in parallel with iNOS in the myocardium during cardiac allograft rejection.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>10653836</pmid><doi>10.1161/01.CIR.101.4.430</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 2000-02, Vol.101 (4), p.430-438 |
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| language | eng |
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| source | MEDLINE; American Heart Association Journals; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Biological and medical sciences Cyclooxygenase 2 Gene Expression Regulation, Enzymologic Graft Rejection - enzymology Graft Rejection - pathology Heart Transplantation - immunology Heart Transplantation - pathology Isoenzymes - genetics Isoenzymes - metabolism Male Medical sciences Nitric Oxide Synthase - genetics Nitric Oxide Synthase - metabolism Nitric Oxide Synthase Type II Prostaglandin-Endoperoxide Synthases - genetics Prostaglandin-Endoperoxide Synthases - metabolism Protein Biosynthesis Rats Rats, Inbred Lew Rats, Inbred WF RNA, Messenger - genetics Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the heart Time Factors Transcription, Genetic Transplantation, Heterotopic Transplantation, Homologous Transplantation, Isogeneic |
| title | Upregulation of COX-2 during cardiac allograft rejection |
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