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Molecular magnetic resonance imaging of myeloperoxidase activity identifies culprit lesions and predicts future atherothrombosis.
Nadel, James; Wang, Xiaoying; Saha, Prakash; Bongers, André; Tumanov, Sergey; Giannotti, Nicola; Chen, Weiyu; Vigder, Niv; Chowdhury, Mohammed M; da Cruz, Gastao Lima; Velasco, Carlos; Prieto, Claudia; Jabbour, Andrew; Botnar, René M; Stocker, Roland; Phinikaridou, Alkystis.
Afiliación
  • Nadel J; Heart Research Institute, Arterial Inflammation and Redox Biology Group, 7 Eliza St, Newtown, Sydney, NSW 2042, Australia.
  • Wang X; Department of Cardiology, St Vincent's Hospital, Sydney, NSW, Australia.
  • Saha P; Department of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
  • Bongers A; School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK.
  • Tumanov S; Academic Department of Surgery, Cardiovascular Division, King's College London, London, UK.
  • Giannotti N; Biological Resources Imaging Laboratory, University of New South Wales, Sydney, NSW, Australia.
  • Chen W; Heart Research Institute, Arterial Inflammation and Redox Biology Group, 7 Eliza St, Newtown, Sydney, NSW 2042, Australia.
  • Vigder N; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
  • Chowdhury MM; Medical Imaging Science, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
  • da Cruz GL; Heart Research Institute, Arterial Inflammation and Redox Biology Group, 7 Eliza St, Newtown, Sydney, NSW 2042, Australia.
  • Velasco C; Heart Research Institute, Arterial Inflammation and Redox Biology Group, 7 Eliza St, Newtown, Sydney, NSW 2042, Australia.
  • Prieto C; Department of Vascular Surgery, University of Cambridge, Cambridge, UK.
  • Jabbour A; Department of Radiology, University of Michigan, Ann Arbor, USA.
  • Botnar RM; School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK.
  • Stocker R; School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK.
  • Phinikaridou A; Pontificia Universidad Católica de Chile, Institute for Biological and Medical Engineering, Santiago, Chile.
Eur Heart J Imaging Methods Pract ; 2(1): qyae004, 2024 Jan.
Article en En | MEDLINE | ID: mdl-38370393
ABSTRACT

Aims:

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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Eur Heart J Imaging Methods Pract Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Eur Heart J Imaging Methods Pract Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido