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Article: Impairment of G-protein-mediated signal transduction in the porcine coronary endothelium during rejection after heart transplantation

TitleImpairment of G-protein-mediated signal transduction in the porcine coronary endothelium during rejection after heart transplantation
Authors
KeywordsAtherosclerosis
Coronary Disease
Endothelial Function
Signal Transduction
Transplantation
Issue Date1999
PublisherOxford University Press. The Journal's web site is located at http://cardiovascres.oxfordjournals.org
Citation
Cardiovascular Research, 1999, v. 43 n. 2, p. 457-470 How to Cite?
AbstractBackground: Endothelial dysfunction is an early event leading to atherosclerosis. It also occurs after orthotopic heart transplantation and can be used to predict the development of intimal hyperplasia in the coronary artery wall. The present study was designed to assess the time course and specific alterations underlying endothelial dysfunction due to rejection after heart transplantation. Methods: A porcine model of heterotopic heart transplantation was used. Preoperative serum typing for the class I antigen of the swine lymphocyte alloantigen was performed to ensure compatibility for this antigen. This permitted survival of the graft with a low grade rejection without immunosuppression. Rings (with or without endothelium) of epicardial coronary arteries of native and transplanted hearts were studied in organ chambers filled with modified Krebs-Ringer bicarbonate solution and compared 1, 30 and 60 days after transplantation. Results: Myocardial contractility was normal in all grafts studied at 60 days after transplantation and all coronary arteries were patent. Myocardial biopsies showed the progression of rejection from day 1 to day 60 after implantation. All endothelium-dependent relaxations were normal one day after transplantation. Endothelium-dependent relaxations to serotonin and to the α2-adrenergic agonist UK14304 (which both activate receptors coupled to Gi-proteins) and to sodium fluoride (a direct activator of G-proteins) were decreased 30 days after transplantation, while those to the calcium ionophore, A23187, and bradykinin were shifted to the right and those to ADP were normal. At 60 days, endothelium-dependent relaxations mediated by the Gi-protein pathway were decreased further while the concentration-relaxation curves to the other agonists were further shifted to the right. Endothelium-independent relaxations to the nitric oxide donor, Sin-1, were progressively reduced at 30 and 60 days, but maximal relaxations were maintained at 60 days. Histomorphometric studies showed a progressive increase in the percentage of coronary rings with intimal thickening from day 1 to day 60 after transplantation. Conclusions: The progressive endothelial dysfunction reported in this model of accelerated coronary atherosclerosis after transplantation without immunosuppression involves preferentially the pertussis-toxin-sensitive Gi-protein-mediated pathway. Endothelium-independent relaxations are decreased at 60 days, as are all other endothelium-dependent relaxations. Decreased endothelium-dependent vasodilatation may contribute to the development of coronary graft vasculopathy.
Persistent Identifierhttp://hdl.handle.net/10722/171229
ISSN
2015 Impact Factor: 5.465
2015 SCImago Journal Rankings: 2.897
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPerrault, LPen_US
dc.contributor.authorBidouard, JPen_US
dc.contributor.authorJaniak, Pen_US
dc.contributor.authorVilleneuve, Nen_US
dc.contributor.authorBruneval, Pen_US
dc.contributor.authorVilaine, JPen_US
dc.contributor.authorVanhoutte, PMen_US
dc.date.accessioned2012-10-30T06:12:49Z-
dc.date.available2012-10-30T06:12:49Z-
dc.date.issued1999en_US
dc.identifier.citationCardiovascular Research, 1999, v. 43 n. 2, p. 457-470en_US
dc.identifier.issn0008-6363en_US
dc.identifier.urihttp://hdl.handle.net/10722/171229-
dc.description.abstractBackground: Endothelial dysfunction is an early event leading to atherosclerosis. It also occurs after orthotopic heart transplantation and can be used to predict the development of intimal hyperplasia in the coronary artery wall. The present study was designed to assess the time course and specific alterations underlying endothelial dysfunction due to rejection after heart transplantation. Methods: A porcine model of heterotopic heart transplantation was used. Preoperative serum typing for the class I antigen of the swine lymphocyte alloantigen was performed to ensure compatibility for this antigen. This permitted survival of the graft with a low grade rejection without immunosuppression. Rings (with or without endothelium) of epicardial coronary arteries of native and transplanted hearts were studied in organ chambers filled with modified Krebs-Ringer bicarbonate solution and compared 1, 30 and 60 days after transplantation. Results: Myocardial contractility was normal in all grafts studied at 60 days after transplantation and all coronary arteries were patent. Myocardial biopsies showed the progression of rejection from day 1 to day 60 after implantation. All endothelium-dependent relaxations were normal one day after transplantation. Endothelium-dependent relaxations to serotonin and to the α2-adrenergic agonist UK14304 (which both activate receptors coupled to Gi-proteins) and to sodium fluoride (a direct activator of G-proteins) were decreased 30 days after transplantation, while those to the calcium ionophore, A23187, and bradykinin were shifted to the right and those to ADP were normal. At 60 days, endothelium-dependent relaxations mediated by the Gi-protein pathway were decreased further while the concentration-relaxation curves to the other agonists were further shifted to the right. Endothelium-independent relaxations to the nitric oxide donor, Sin-1, were progressively reduced at 30 and 60 days, but maximal relaxations were maintained at 60 days. Histomorphometric studies showed a progressive increase in the percentage of coronary rings with intimal thickening from day 1 to day 60 after transplantation. Conclusions: The progressive endothelial dysfunction reported in this model of accelerated coronary atherosclerosis after transplantation without immunosuppression involves preferentially the pertussis-toxin-sensitive Gi-protein-mediated pathway. Endothelium-independent relaxations are decreased at 60 days, as are all other endothelium-dependent relaxations. Decreased endothelium-dependent vasodilatation may contribute to the development of coronary graft vasculopathy.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://cardiovascres.oxfordjournals.orgen_US
dc.relation.ispartofCardiovascular Researchen_US
dc.subjectAtherosclerosis-
dc.subjectCoronary Disease-
dc.subjectEndothelial Function-
dc.subjectSignal Transduction-
dc.subjectTransplantation-
dc.subject.meshAdenosine Diphosphate - Pharmacologyen_US
dc.subject.meshAnalysis Of Varianceen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBradykinin - Pharmacologyen_US
dc.subject.meshCalcimycin - Pharmacologyen_US
dc.subject.meshCoronary Artery Disease - Metabolism - Pathologyen_US
dc.subject.meshCoronary Vessels - Drug Effects - Ultrastructureen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshEndothelium, Vascular - Drug Effects - Metabolismen_US
dc.subject.meshFemaleen_US
dc.subject.meshGtp-Binding Proteins - Metabolismen_US
dc.subject.meshGraft Rejectionen_US
dc.subject.meshHeart Transplantationen_US
dc.subject.meshIonophores - Pharmacologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMicroscopy, Electronen_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshSwineen_US
dc.subject.meshTransplantation, Homologousen_US
dc.titleImpairment of G-protein-mediated signal transduction in the porcine coronary endothelium during rejection after heart transplantationen_US
dc.typeArticleen_US
dc.identifier.emailVanhoutte, PM:vanhoutt@hku.hken_US
dc.identifier.authorityVanhoutte, PM=rp00238en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/S0008-6363(99)00101-7en_US
dc.identifier.pmid10536676-
dc.identifier.scopuseid_2-s2.0-0033179526en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033179526&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume43en_US
dc.identifier.issue2en_US
dc.identifier.spage457en_US
dc.identifier.epage470en_US
dc.identifier.isiWOS:000081747400026-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridPerrault, LP=7004370552en_US
dc.identifier.scopusauthoridBidouard, JP=6601955808en_US
dc.identifier.scopusauthoridJaniak, P=6603686655en_US
dc.identifier.scopusauthoridVilleneuve, N=7003458215en_US
dc.identifier.scopusauthoridBruneval, P=35414804500en_US
dc.identifier.scopusauthoridVilaine, JP=7004617134en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US

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