Imaging Granzyme B activity assesses immune-mediated myocarditis

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dc.contributor.authorKonishi, Masanori
dc.contributor.authorErdem, Sultan Sibel
dc.contributor.authorWeissleder, Ralph
dc.contributor.authorLichtman, Andrew
dc.contributor.authorMcCarthy, Jason
dc.contributor.authorLibby, Peter
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T19:51:09Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T19:51:09Z
dc.date.issued2015
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyokimya Ana Bilim Dalı
dc.descriptionWOS: 000360142000006
dc.descriptionPubMed ID: 26199323
dc.description.abstractRationale: The development of molecular imaging approaches that assess specific immunopathologic mechanisms can advance the study of myocarditis. Objective: This study validates a novel molecular imaging tool that enables the in vivo visualization of granzyme B activity, a major effector of cytotoxic CD8(+) T lymphocytes. Methods and Results: We synthesized and optimized a fluorogenic substrate capable of reporting on granzyme B activity and examined its specificity ex vivo in mice hearts with experimental cytotoxic CD8(+) T lymphocyte-mediated myocarditis using fluorescence reflectance imaging, validated by histological examination. In vivo experiments localized granzyme B activity in hearts with acute myocarditis monitored by fluorescent molecular tomography in conjunction with coregistered computed tomography imaging. A model anti-inflammatory intervention (dexamethasone administration) in vivo reduced granzyme B activity (vehicle versus dexamethasone: 504263 versus 194 +/- 77 fluorescence intensities in hearts; P=0.002). Conclusions: Molecular imaging of granzyme B activity can visualize T cell-mediated myocardial injury and monitor the response to an anti-inflammatory intervention.
dc.description.sponsorshipNational Institutes of Health National Heart, Lung, and Blood Institute contract [HHSN268201000044C, R01HL121363-01]; National Institutes of Health; Translational Program of Excellence in Nanotechnology; Japan Society for the Promotion of Science; Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation; Uehara Memorial Foundationen_US
dc.description.sponsorshipThis study was supported, in part, by National Institutes of Health National Heart, Lung, and Blood Institute contract HHSN268201000044C and R01HL121363-01, Grant-in-Aid for Scientific Research from the National Institutes of Health; Translational Program of Excellence in Nanotechnology, Japan Society for the Promotion of Science; Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation, and The Uehara Memorial Foundation; Research Fellowship.en_US
dc.identifier.citationKonishi, M., Erdem, S. S., Weissleder, R., Lichtman, A., McCarthy, J. ve Libby, P. (2015). Imaging Granzyme B activity assesses immune-mediated myocarditis. Circulation Research, 117(6), 502-512. https://dx.doi.org/10.1161/CIRCRESAHA.115.306364
dc.identifier.doi10.1161/CIRCRESAHA.115.306364
dc.identifier.endpage512
dc.identifier.issn0009-7330
dc.identifier.issn1524-4571
dc.identifier.issue6
dc.identifier.scopusqualityQ1
dc.identifier.startpage502
dc.identifier.urihttps://dx.doi.org/10.1161/CIRCRESAHA.115.306364
dc.identifier.urihttps://hdl.handle.net/20.500.12511/2158
dc.identifier.volume117
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherLippincott Williams and Wilkins
dc.relation.ispartofCirculation Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectDexamethasone
dc.subjectGranzyme
dc.subjectImmunology
dc.subjectMolecular Imaging
dc.subjectMyocarditis
dc.titleImaging Granzyme B activity assesses immune-mediated myocarditis
dc.typeArticle

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