Molecular magnetic resonance imaging of myeloperoxidase activity identifies culprit lesions and predicts future atherothrombosis

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dc.catalogadorvzp
dc.contributor.authorNadel, James
dc.contributor.authorWang, Xiaoying
dc.contributor.authorSaha, Prakash
dc.contributor.authorBongers, André
dc.contributor.authorTumanov, Sergey
dc.contributor.authorGiannotti, Nicola
dc.contributor.authorChen, Weiyu
dc.contributor.authorVigder, Niv
dc.contributor.authorChowdhury, Mohammed
dc.contributor.authorLima da Cruz, Gastao
dc.contributor.authorVelasco Jimeno, Carlos
dc.contributor.authorPrieto Vasquez, Claudia
dc.contributor.authorJabbour, Andrew
dc.contributor.authorBotnar, Rene Michael
dc.contributor.authorStocker, Roland
dc.contributor.authorPhinikaridou, Alkystis
dc.date.accessioned2025-10-02T14:00:03Z
dc.date.available2025-10-02T14:00:03Z
dc.date.issued2024
dc.description.abstractAims Unstable atherosclerotic plaques have increased activity of myeloperoxidase (MPO). We examined whether molecular magnetic resonance imaging (MRI) of intraplaque MPO activity predicts future atherothrombosis in rabbits and correlates with ruptured human atheroma. Methods and results Plaque MPO activity was assessed in vivo in rabbits (n = 12) using the MPO-gadolinium (Gd) probe at 8 and 12 weeks after induction of atherosclerosis and before pharmacological triggering of atherothrombosis. Excised plaques were used to confirm MPO activity by liquid chromatography–tandem mass spectrometry (LC–MSMS) and to determine MPO distribution by histology. MPO activity was higher in plaques that caused post-trigger atherothrombosis than plaques that did not. Among the in vivo MRI metrics, the plaques’ R1 relaxation rate after administration of MPO-Gd was the best predictor of atherothrombosis. MPO activity measured in human carotid endarterectomy specimens (n = 30) by MPO-Gd–enhanced MRI was correlated with in vivo patient MRI and histological plaque phenotyping, as well as LC–MSMS. MPO-Gd retention measured as the change in R1 relaxation from baseline was significantly greater in histologic and MRI-graded American Heart Association (AHA) type VI than type III–V plaques. This association was confirmed by comparing AHA grade to MPO activity determined by LC–MSMS. Conclusion We show that elevated intraplaque MPO activity detected by molecular MRI employing MPO-Gd predicts future atherothrombosis in a rabbit model and detects ruptured human atheroma, strengthening the translational potential of this approach to prospectively detect high-risk atherosclerosis.
dc.fechaingreso.objetodigital2025-10-02
dc.format.extent10 páginas
dc.fuente.origenORCID
dc.identifier.doi10.1093/ehjimp/qyae004
dc.identifier.eissn2755-9637
dc.identifier.urihttps://doi.org/10.1093/ehjimp/qyae004
dc.identifier.urihttps://kclpure.kcl.ac.uk/portal/en/publications/91f9bc6f-13a3-45f5-99c4-7624d438a8b7
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/105872
dc.information.autorucInstituto de Ingeniería Biológica y Médica; Botnar, Rene Michael; 0000-0003-2811-2509; 1015313
dc.issue.numero1
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final10
dc.pagina.inicio1
dc.revistaEuropean Heart Journal - Imaging Methods and Practice
dc.rightsacceso abierto
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAtherosclerosis
dc.subjectAtherothrombosis
dc.subjectCarotid endarterectomy
dc.subjectMolecular magnetic resonance imaging
dc.subjectMyeloperoxidase
dc.subjectPlaque disruption
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleMolecular magnetic resonance imaging of myeloperoxidase activity identifies culprit lesions and predicts future atherothrombosis
dc.typeartículo
dc.volumen2
sipa.codpersvinculados1015313
sipa.trazabilidadORCID;2025-09-29
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