Imaging Macrophage and Hematopoietic Progenitor Proliferation in Atherosclerosis
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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.
In: Circulation Research, Vol. 117, No. 10, 2015, p. 835-45.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Imaging Macrophage and Hematopoietic Progenitor Proliferation in Atherosclerosis
AU - Ye, Yu-Xiang
AU - Calcagno, Claudia
AU - Binderup, Tina
AU - Courties, Gabriel
AU - Keliher, Edmund J
AU - Wojtkiewicz, Gregory R
AU - Iwamoto, Yoshiko
AU - Tang, Jun
AU - Pérez-Medina, Carlos
AU - Mani, Venkatesh
AU - Ishino, Seigo
AU - Johnbeck, Camilla Bardram
AU - Knigge, Ulrich
AU - Fayad, Zahi A
AU - Libby, Peter
AU - Weissleder, Ralph
AU - Tawakol, Ahmed
AU - Dubey, Shipra
AU - Belanger, Anthony P
AU - Di Carli, Marcelo F
AU - Swirski, Filip K
AU - Kjaer, Andreas
AU - Mulder, Willem J M
AU - Nahrendorf, Matthias
N1 - © 2015 American Heart Association, Inc.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Animals
KW - Aorta, Thoracic
KW - Aortic Diseases
KW - Apolipoproteins E
KW - Atherosclerosis
KW - Bone Marrow
KW - Carotid Artery Diseases
KW - Cell Proliferation
KW - Cholesterol, Dietary
KW - Dideoxynucleosides
KW - Diet, High-Fat
KW - Disease Models, Animal
KW - Female
KW - Fluorodeoxyglucose F18
KW - Hematopoietic Stem Cells
KW - Humans
KW - Macrophages
KW - Male
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Multimodal Imaging
KW - Plaque, Atherosclerotic
KW - Positron-Emission Tomography
KW - Predictive Value of Tests
KW - Rabbits
KW - Radiopharmaceuticals
KW - Retrospective Studies
KW - Spleen
KW - Time Factors
KW - Tomography, X-Ray Computed
U2 - 10.1161/CIRCRESAHA.115.307024
DO - 10.1161/CIRCRESAHA.115.307024
M3 - Journal article
C2 - 26394773
VL - 117
SP - 835
EP - 845
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 10
ER -
ID: 162683446