Decreased Transplant Arteriosclerosis in Endothelial Nitric Oxide Synthase-Deficient Mice
Occlusive vascular changes, characterized by the formation of a neointima with lumen obstruction, are key histologic findings of allograft arteriosclerosis. Vascular integrity of the graft is critically dependent on nitric oxide (NO), synthesized by NO synthases (NOS), of which three isoforms have b...
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Veröffentlicht in: | Transplantation 2010-03, Vol.89 (5), p.518-526 |
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creator | HONG, Zebger-Gong KAMPMANN, Jan QUERFELD, Uwe LINGHUA KONG ROIGAS, Jan SOMMER, Kerstin HOFF, Uwe KRÄMER, Stephanie PETERS, Harm MÜLLER, Dominik DRAGUN, Duska |
description | Occlusive vascular changes, characterized by the formation of a neointima with lumen obstruction, are key histologic findings of allograft arteriosclerosis. Vascular integrity of the graft is critically dependent on nitric oxide (NO), synthesized by NO synthases (NOS), of which three isoforms have been located in the arterial wall: endothelial NOS (eNOS), inducible NOS, and neuronal NOS (nNOS). We have studied the role of NOS in a murine model of aortic allograft rejection.
The descending thoracic aorta of donor mice (BALB/c mice) was transplanted into two groups of recipients: (a) C57BL/6J and (b) C57BL/6J mice homozygous (-/-) for a knockout of the eNOS gene (eNOS(-/-)).
After 4 weeks, pronounced neointima formation, upregulated expression of adhesion molecules, and increased infiltration by inflammatory cells were demonstrated in wild-type recipient mice, whereas eNOS(-/-) recipient mice were protected from neointima development by a significantly increased synthesis of NO, as shown by increased formation of cGMP; this was mainly explained by upregulation of inducible NOS and nNOS.
Upregulation of inducible NOS and nNOS isoforms may be beneficial in preventing allograft arteriosclerosis in the early posttransplant period. |
doi_str_mv | 10.1097/TP.0b013e3181c7dce4 |
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The descending thoracic aorta of donor mice (BALB/c mice) was transplanted into two groups of recipients: (a) C57BL/6J and (b) C57BL/6J mice homozygous (-/-) for a knockout of the eNOS gene (eNOS(-/-)).
After 4 weeks, pronounced neointima formation, upregulated expression of adhesion molecules, and increased infiltration by inflammatory cells were demonstrated in wild-type recipient mice, whereas eNOS(-/-) recipient mice were protected from neointima development by a significantly increased synthesis of NO, as shown by increased formation of cGMP; this was mainly explained by upregulation of inducible NOS and nNOS.
Upregulation of inducible NOS and nNOS isoforms may be beneficial in preventing allograft arteriosclerosis in the early posttransplant period.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/TP.0b013e3181c7dce4</identifier><identifier>PMID: 20019649</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Aorta, Thoracic - transplantation ; Arteriosclerosis - prevention & control ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cell Adhesion ; Cell Division ; Cyclic GMP - metabolism ; DNA Primers ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Homozygote ; Kidney - enzymology ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout - genetics ; Myocardium - enzymology ; Nitric Oxide - metabolism ; Nitric Oxide Synthase Type I - genetics ; Nitric Oxide Synthase Type III - deficiency ; Nitric Oxide Synthase Type III - genetics ; Postoperative Complications - prevention & control ; Reverse Transcriptase Polymerase Chain Reaction ; RNA - genetics ; RNA - isolation & purification ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Tissue, organ and graft immunology ; Tunica Intima - pathology</subject><ispartof>Transplantation, 2010-03, Vol.89 (5), p.518-526</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-37bbd6f7b12aca39dd9822db0dbb3522f23f6922f201d1296150450145afb77e3</citedby><cites>FETCH-LOGICAL-c411t-37bbd6f7b12aca39dd9822db0dbb3522f23f6922f201d1296150450145afb77e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22540346$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20019649$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HONG, Zebger-Gong</creatorcontrib><creatorcontrib>KAMPMANN, Jan</creatorcontrib><creatorcontrib>QUERFELD, Uwe</creatorcontrib><creatorcontrib>LINGHUA KONG</creatorcontrib><creatorcontrib>ROIGAS, Jan</creatorcontrib><creatorcontrib>SOMMER, Kerstin</creatorcontrib><creatorcontrib>HOFF, Uwe</creatorcontrib><creatorcontrib>KRÄMER, Stephanie</creatorcontrib><creatorcontrib>PETERS, Harm</creatorcontrib><creatorcontrib>MÜLLER, Dominik</creatorcontrib><creatorcontrib>DRAGUN, Duska</creatorcontrib><title>Decreased Transplant Arteriosclerosis in Endothelial Nitric Oxide Synthase-Deficient Mice</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>Occlusive vascular changes, characterized by the formation of a neointima with lumen obstruction, are key histologic findings of allograft arteriosclerosis. Vascular integrity of the graft is critically dependent on nitric oxide (NO), synthesized by NO synthases (NOS), of which three isoforms have been located in the arterial wall: endothelial NOS (eNOS), inducible NOS, and neuronal NOS (nNOS). We have studied the role of NOS in a murine model of aortic allograft rejection.
The descending thoracic aorta of donor mice (BALB/c mice) was transplanted into two groups of recipients: (a) C57BL/6J and (b) C57BL/6J mice homozygous (-/-) for a knockout of the eNOS gene (eNOS(-/-)).
After 4 weeks, pronounced neointima formation, upregulated expression of adhesion molecules, and increased infiltration by inflammatory cells were demonstrated in wild-type recipient mice, whereas eNOS(-/-) recipient mice were protected from neointima development by a significantly increased synthesis of NO, as shown by increased formation of cGMP; this was mainly explained by upregulation of inducible NOS and nNOS.
Upregulation of inducible NOS and nNOS isoforms may be beneficial in preventing allograft arteriosclerosis in the early posttransplant period.</description><subject>Animals</subject><subject>Aorta, Thoracic - transplantation</subject><subject>Arteriosclerosis - prevention & control</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cell Adhesion</subject><subject>Cell Division</subject><subject>Cyclic GMP - metabolism</subject><subject>DNA Primers</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Homozygote</subject><subject>Kidney - enzymology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout - genetics</subject><subject>Myocardium - enzymology</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric Oxide Synthase Type I - genetics</subject><subject>Nitric Oxide Synthase Type III - deficiency</subject><subject>Nitric Oxide Synthase Type III - genetics</subject><subject>Postoperative Complications - prevention & control</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA - genetics</subject><subject>RNA - isolation & purification</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Tissue, organ and graft immunology</subject><subject>Tunica Intima - pathology</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLxDAUhYMoOj5-gSDdiKvqvUnatEvxDb7AceGq5HGLkU47Jh3Qf2_EUcGNq7P5zrncj7FdhEOEWh1N7w_BAAoSWKFVzpJcYRMshMxLqGCVTQAk5iiE2mCbMb4AQCGUWmcbHADrUtYT9nRKNpCO5LJp0H2cd7ofs-MwUvBDtB2FIfqY-T47690wPlPndZfd-jF4m929eUfZw3s_PqeF_JRabz2l_o23tM3WWt1F2lnmFns8P5ueXObXdxdXJ8fXuZWIYy6UMa5slUGurRa1c3XFuTPgjBEF5y0XbVl_JqBDXpdYgCwAZaFboxSJLXbwtTsPw-uC4tjMfLTUpUdoWMRGyTLRdVX-TwqRLlWySKT4Im16PwZqm3nwMx3eG4TmU34zvW_-yk-tveX-wszI_XS-bSdgfwnoaHXXJuHWx1-OFxKELMUHnF2ONg</recordid><startdate>20100315</startdate><enddate>20100315</enddate><creator>HONG, Zebger-Gong</creator><creator>KAMPMANN, Jan</creator><creator>QUERFELD, Uwe</creator><creator>LINGHUA KONG</creator><creator>ROIGAS, Jan</creator><creator>SOMMER, Kerstin</creator><creator>HOFF, Uwe</creator><creator>KRÄMER, Stephanie</creator><creator>PETERS, Harm</creator><creator>MÜLLER, Dominik</creator><creator>DRAGUN, Duska</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>7T5</scope><scope>H94</scope></search><sort><creationdate>20100315</creationdate><title>Decreased Transplant Arteriosclerosis in Endothelial Nitric Oxide Synthase-Deficient Mice</title><author>HONG, Zebger-Gong ; KAMPMANN, Jan ; QUERFELD, Uwe ; LINGHUA KONG ; ROIGAS, Jan ; SOMMER, Kerstin ; HOFF, Uwe ; KRÄMER, Stephanie ; PETERS, Harm ; MÜLLER, Dominik ; DRAGUN, Duska</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-37bbd6f7b12aca39dd9822db0dbb3522f23f6922f201d1296150450145afb77e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Aorta, Thoracic - transplantation</topic><topic>Arteriosclerosis - prevention & control</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cell Adhesion</topic><topic>Cell Division</topic><topic>Cyclic GMP - metabolism</topic><topic>DNA Primers</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Homozygote</topic><topic>Kidney - enzymology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout - genetics</topic><topic>Myocardium - enzymology</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric Oxide Synthase Type I - genetics</topic><topic>Nitric Oxide Synthase Type III - deficiency</topic><topic>Nitric Oxide Synthase Type III - genetics</topic><topic>Postoperative Complications - prevention & control</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA - genetics</topic><topic>RNA - isolation & purification</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Tissue, organ and graft immunology</topic><topic>Tunica Intima - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HONG, Zebger-Gong</creatorcontrib><creatorcontrib>KAMPMANN, Jan</creatorcontrib><creatorcontrib>QUERFELD, Uwe</creatorcontrib><creatorcontrib>LINGHUA KONG</creatorcontrib><creatorcontrib>ROIGAS, Jan</creatorcontrib><creatorcontrib>SOMMER, Kerstin</creatorcontrib><creatorcontrib>HOFF, Uwe</creatorcontrib><creatorcontrib>KRÄMER, Stephanie</creatorcontrib><creatorcontrib>PETERS, Harm</creatorcontrib><creatorcontrib>MÜLLER, Dominik</creatorcontrib><creatorcontrib>DRAGUN, Duska</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HONG, Zebger-Gong</au><au>KAMPMANN, Jan</au><au>QUERFELD, Uwe</au><au>LINGHUA KONG</au><au>ROIGAS, Jan</au><au>SOMMER, Kerstin</au><au>HOFF, Uwe</au><au>KRÄMER, Stephanie</au><au>PETERS, Harm</au><au>MÜLLER, Dominik</au><au>DRAGUN, Duska</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased Transplant Arteriosclerosis in Endothelial Nitric Oxide Synthase-Deficient Mice</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2010-03-15</date><risdate>2010</risdate><volume>89</volume><issue>5</issue><spage>518</spage><epage>526</epage><pages>518-526</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>Occlusive vascular changes, characterized by the formation of a neointima with lumen obstruction, are key histologic findings of allograft arteriosclerosis. Vascular integrity of the graft is critically dependent on nitric oxide (NO), synthesized by NO synthases (NOS), of which three isoforms have been located in the arterial wall: endothelial NOS (eNOS), inducible NOS, and neuronal NOS (nNOS). We have studied the role of NOS in a murine model of aortic allograft rejection.
The descending thoracic aorta of donor mice (BALB/c mice) was transplanted into two groups of recipients: (a) C57BL/6J and (b) C57BL/6J mice homozygous (-/-) for a knockout of the eNOS gene (eNOS(-/-)).
After 4 weeks, pronounced neointima formation, upregulated expression of adhesion molecules, and increased infiltration by inflammatory cells were demonstrated in wild-type recipient mice, whereas eNOS(-/-) recipient mice were protected from neointima development by a significantly increased synthesis of NO, as shown by increased formation of cGMP; this was mainly explained by upregulation of inducible NOS and nNOS.
Upregulation of inducible NOS and nNOS isoforms may be beneficial in preventing allograft arteriosclerosis in the early posttransplant period.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>20019649</pmid><doi>10.1097/TP.0b013e3181c7dce4</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Aorta, Thoracic - transplantation Arteriosclerosis - prevention & control Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cell Adhesion Cell Division Cyclic GMP - metabolism DNA Primers Fundamental and applied biological sciences. Psychology Fundamental immunology Homozygote Kidney - enzymology Medical sciences Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout - genetics Myocardium - enzymology Nitric Oxide - metabolism Nitric Oxide Synthase Type I - genetics Nitric Oxide Synthase Type III - deficiency Nitric Oxide Synthase Type III - genetics Postoperative Complications - prevention & control Reverse Transcriptase Polymerase Chain Reaction RNA - genetics RNA - isolation & purification Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Tissue, organ and graft immunology Tunica Intima - pathology |
title | Decreased Transplant Arteriosclerosis in Endothelial Nitric Oxide Synthase-Deficient Mice |
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