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Imaging Macrophage and Hematopoietic Progenitor Proliferation in Atherosclerosis.
Ye, Yu-Xiang; Calcagno, Claudia; Binderup, Tina; Courties, Gabriel; Keliher, Edmund J; Wojtkiewicz, Gregory R; Iwamoto, Yoshiko; Tang, Jun; Pérez-Medina, Carlos; Mani, Venkatesh; Ishino, Seigo; Johnbeck, Camilla Bardram; Knigge, Ulrich; Fayad, Zahi A; Libby, Peter; Weissleder, Ralph; Tawakol, Ahmed; Dubey, Shipra; Belanger, Anthony P; Di Carli, Marcelo F; Swirski, Filip K; Kjaer, Andreas; Mulder, Willem J M; Nahrendorf, Matthias.
Afiliación
  • Ye YX; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Calcagno C; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Binderup T; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Courties G; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Keliher EJ; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Wojtkiewicz GR; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Iwamoto Y; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Tang J; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Pérez-Medina C; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Mani V; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Ishino S; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Johnbeck CB; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Knigge U; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Fayad ZA; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Libby P; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Weissleder R; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Tawakol A; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Dubey S; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Belanger AP; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Di Carli MF; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Swirski FK; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Kjaer A; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Mulder WJ; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
  • Nahrendorf M; From the Center for Systems Biology, Department of Radiology (Y.-X.Y., G.C., E.J.K., G.R.W., Y.I., R.W., F.K.S., M.N.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; Translational and Molecular Imaging Institute, Department of Radiology, Icahn S
Circ Res ; 117(10): 835-45, 2015 Oct 23.
Article en En | MEDLINE | ID: mdl-26394773
ABSTRACT
RATIONALE Local plaque macrophage proliferation and monocyte production in hematopoietic organs promote progression of atherosclerosis. Therefore, noninvasive imaging of proliferation could serve as a biomarker and monitor therapeutic intervention.

OBJECTIVE:

To explore (18)F-FLT positron emission tomography-computed tomography imaging of cell proliferation in atherosclerosis. METHODS AND

RESULTS:

(18)F-FLT positron emission tomography-computed tomography was performed in mice, rabbits, and humans with atherosclerosis. In apolipoprotein E knock out mice, increased (18)F-FLT signal was observed in atherosclerotic lesions, spleen, and bone marrow (standardized uptake values wild-type versus apolipoprotein E knock out mice, 0.05 ± 0.01 versus 0.17 ± 0.01, P<0.05 in aorta; 0.13 ± 0.01 versus 0.28 ± 0.02, P<0.05 in bone marrow; 0.06 ± 0.01 versus 0.22 ± 0.01, P<0.05 in spleen), corroborated by ex vivo scintillation counting and autoradiography. Flow cytometry confirmed significantly higher proliferation of macrophages in aortic lesions and hematopoietic stem and progenitor cells in the spleen and bone marrow in these mice. In addition, (18)F-FLT plaque signal correlated with the duration of high cholesterol diet (r(2)=0.33, P<0.05). Aortic (18)F-FLT uptake was reduced when cell proliferation was suppressed with fluorouracil in apolipoprotein E knock out mice (P<0.05). In rabbits, inflamed atherosclerotic vasculature with the highest (18)F-fluorodeoxyglucose uptake enriched (18)F-FLT. In patients with atherosclerosis, (18)F-FLT signal significantly increased in the inflamed carotid artery and in the aorta.

CONCLUSIONS:

(18)F-FLT positron emission tomography imaging may serve as an imaging biomarker for cell proliferation in plaque and hematopoietic activity in individuals with atherosclerosis.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Enfermedades de la Aorta / Células Madre Hematopoyéticas / Enfermedades de las Arterias Carótidas / Tomografía Computarizada por Rayos X / Tomografía de Emisión de Positrones / Proliferación Celular / Aterosclerosis / Macrófagos Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Circ Res Año: 2015 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Enfermedades de la Aorta / Células Madre Hematopoyéticas / Enfermedades de las Arterias Carótidas / Tomografía Computarizada por Rayos X / Tomografía de Emisión de Positrones / Proliferación Celular / Aterosclerosis / Macrófagos Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Circ Res Año: 2015 Tipo del documento: Article