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
Hauptverfasser: HONG, Zebger-Gong, KAMPMANN, Jan, QUERFELD, Uwe, LINGHUA KONG, ROIGAS, Jan, SOMMER, Kerstin, HOFF, Uwe, KRÄMER, Stephanie, PETERS, Harm, MÜLLER, Dominik, DRAGUN, Duska
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container_end_page 526
container_issue 5
container_start_page 518
container_title Transplantation
container_volume 89
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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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. 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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 &amp; control ; Reverse Transcriptase Polymerase Chain Reaction ; RNA - genetics ; RNA - isolation &amp; purification ; Surgery (general aspects). Transplantations, organ and tissue grafts. 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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 &amp; 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 &amp; control</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA - genetics</subject><subject>RNA - isolation &amp; 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 &amp; 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 &amp; control</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. 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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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