PET/MRI of inflammation in myocardial infarction

W.W. Lee, B. Marinelli, A.M. van der Laan, B.F. Sena, R. Gorbatov, F. Leuschner, P. Dutta, Y. Iwamoto, T. Ueno, M.P.V. Begieneman, H.W.M. Niessen, J.J. Piek, C. Vinegoni, M.J. Pittet, F.K. Swirski, A. Tawakol, M. di Carli, R. Weissleder, M. Nahrendorf

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVES: The aim of this study was to explore post-myocardial infarction (MI) myocardial inflammation.

BACKGROUND: Innate immune cells are centrally involved in infarct healing and are emerging therapeutic targets in cardiovascular disease; however, clinical tools to assess their presence in tissue are scarce. Furthermore, it is currently not known if the nonischemic remote zone recruits monocytes.

METHODS: Acute inflammation was followed in mice with coronary ligation by 18-fluorodeoxyglucose ((18)FDG) positron emission tomography/magnetic resonance imaging, fluorescence-activated cell sorting, polymerase chain reaction, and histology.

RESULTS: Gd-DTPA-enhanced infarcts showed high (18)FDG uptake on day 5 after MI. Cell depletion and isolation data confirmed that this largely reflected inflammation; CD11b(+) cells had 4-fold higher (18)FDG uptake than the infarct tissue from which they were isolated (p < 0.01). Surprisingly, there was considerable monocyte recruitment in the remote myocardium (approximately 10(4)/mg of myocardium, 5.6-fold increase; p < 0.01), a finding mirrored by macrophage infiltration in the remote myocardium of patients with acute MI. Temporal kinetics of cell recruitment were slower than in the infarct, with peak numbers on day 10 after ischemia. Quantitative polymerase chain reaction showed a robust increase of recruiting adhesion molecules and chemokines in the remote myocardium (e.g., 12-fold increase of monocyte chemoattractant protein-1), although levels were always lower than in the infarct. Finally, matrix metalloproteinase activity was significantly increased in noninfarcted myocardium, suggesting that monocyte recruitment to the remote zone may contribute to post-MI dilation.

CONCLUSIONS: This study shed light on the innate inflammatory response in remote myocardium after MI.

Original languageEnglish
Pages (from-to)153-163
Number of pages11
JournalJournal of the American College of Cardiology
Volume59
Issue number2
DOIs
Publication statusPublished - 10 Jan 2012

Cite this

Lee, W. W., Marinelli, B., van der Laan, A. M., Sena, B. F., Gorbatov, R., Leuschner, F., ... Nahrendorf, M. (2012). PET/MRI of inflammation in myocardial infarction. Journal of the American College of Cardiology, 59(2), 153-163. https://doi.org/10.1016/j.jacc.2011.08.066
Lee, W.W. ; Marinelli, B. ; van der Laan, A.M. ; Sena, B.F. ; Gorbatov, R. ; Leuschner, F. ; Dutta, P. ; Iwamoto, Y. ; Ueno, T. ; Begieneman, M.P.V. ; Niessen, H.W.M. ; Piek, J.J. ; Vinegoni, C. ; Pittet, M.J. ; Swirski, F.K. ; Tawakol, A. ; di Carli, M. ; Weissleder, R. ; Nahrendorf, M. / PET/MRI of inflammation in myocardial infarction. In: Journal of the American College of Cardiology. 2012 ; Vol. 59, No. 2. pp. 153-163.
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title = "PET/MRI of inflammation in myocardial infarction",
abstract = "OBJECTIVES: The aim of this study was to explore post-myocardial infarction (MI) myocardial inflammation.BACKGROUND: Innate immune cells are centrally involved in infarct healing and are emerging therapeutic targets in cardiovascular disease; however, clinical tools to assess their presence in tissue are scarce. Furthermore, it is currently not known if the nonischemic remote zone recruits monocytes.METHODS: Acute inflammation was followed in mice with coronary ligation by 18-fluorodeoxyglucose ((18)FDG) positron emission tomography/magnetic resonance imaging, fluorescence-activated cell sorting, polymerase chain reaction, and histology.RESULTS: Gd-DTPA-enhanced infarcts showed high (18)FDG uptake on day 5 after MI. Cell depletion and isolation data confirmed that this largely reflected inflammation; CD11b(+) cells had 4-fold higher (18)FDG uptake than the infarct tissue from which they were isolated (p < 0.01). Surprisingly, there was considerable monocyte recruitment in the remote myocardium (approximately 10(4)/mg of myocardium, 5.6-fold increase; p < 0.01), a finding mirrored by macrophage infiltration in the remote myocardium of patients with acute MI. Temporal kinetics of cell recruitment were slower than in the infarct, with peak numbers on day 10 after ischemia. Quantitative polymerase chain reaction showed a robust increase of recruiting adhesion molecules and chemokines in the remote myocardium (e.g., 12-fold increase of monocyte chemoattractant protein-1), although levels were always lower than in the infarct. Finally, matrix metalloproteinase activity was significantly increased in noninfarcted myocardium, suggesting that monocyte recruitment to the remote zone may contribute to post-MI dilation.CONCLUSIONS: This study shed light on the innate inflammatory response in remote myocardium after MI.",
keywords = "Aged, Animals, Case-Control Studies, Female, Fluorodeoxyglucose F18, Humans, Macrophages, Magnetic Resonance Imaging, Male, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Mice, Middle Aged, Monocytes, Myocardial Infarction, Myocarditis, Positron-Emission Tomography, Radiopharmaceuticals, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "W.W. Lee and B. Marinelli and {van der Laan}, A.M. and B.F. Sena and R. Gorbatov and F. Leuschner and P. Dutta and Y. Iwamoto and T. Ueno and M.P.V. Begieneman and H.W.M. Niessen and J.J. Piek and C. Vinegoni and M.J. Pittet and F.K. Swirski and A. Tawakol and {di Carli}, M. and R. Weissleder and M. Nahrendorf",
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Lee, WW, Marinelli, B, van der Laan, AM, Sena, BF, Gorbatov, R, Leuschner, F, Dutta, P, Iwamoto, Y, Ueno, T, Begieneman, MPV, Niessen, HWM, Piek, JJ, Vinegoni, C, Pittet, MJ, Swirski, FK, Tawakol, A, di Carli, M, Weissleder, R & Nahrendorf, M 2012, 'PET/MRI of inflammation in myocardial infarction' Journal of the American College of Cardiology, vol. 59, no. 2, pp. 153-163. https://doi.org/10.1016/j.jacc.2011.08.066

PET/MRI of inflammation in myocardial infarction. / Lee, W.W.; Marinelli, B.; van der Laan, A.M.; Sena, B.F.; Gorbatov, R.; Leuschner, F.; Dutta, P.; Iwamoto, Y.; Ueno, T.; Begieneman, M.P.V.; Niessen, H.W.M.; Piek, J.J.; Vinegoni, C.; Pittet, M.J.; Swirski, F.K.; Tawakol, A.; di Carli, M.; Weissleder, R.; Nahrendorf, M.

In: Journal of the American College of Cardiology, Vol. 59, No. 2, 10.01.2012, p. 153-163.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - PET/MRI of inflammation in myocardial infarction

AU - Lee, W.W.

AU - Marinelli, B.

AU - van der Laan, A.M.

AU - Sena, B.F.

AU - Gorbatov, R.

AU - Leuschner, F.

AU - Dutta, P.

AU - Iwamoto, Y.

AU - Ueno, T.

AU - Begieneman, M.P.V.

AU - Niessen, H.W.M.

AU - Piek, J.J.

AU - Vinegoni, C.

AU - Pittet, M.J.

AU - Swirski, F.K.

AU - Tawakol, A.

AU - di Carli, M.

AU - Weissleder, R.

AU - Nahrendorf, M.

N1 - Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

PY - 2012/1/10

Y1 - 2012/1/10

N2 - OBJECTIVES: The aim of this study was to explore post-myocardial infarction (MI) myocardial inflammation.BACKGROUND: Innate immune cells are centrally involved in infarct healing and are emerging therapeutic targets in cardiovascular disease; however, clinical tools to assess their presence in tissue are scarce. Furthermore, it is currently not known if the nonischemic remote zone recruits monocytes.METHODS: Acute inflammation was followed in mice with coronary ligation by 18-fluorodeoxyglucose ((18)FDG) positron emission tomography/magnetic resonance imaging, fluorescence-activated cell sorting, polymerase chain reaction, and histology.RESULTS: Gd-DTPA-enhanced infarcts showed high (18)FDG uptake on day 5 after MI. Cell depletion and isolation data confirmed that this largely reflected inflammation; CD11b(+) cells had 4-fold higher (18)FDG uptake than the infarct tissue from which they were isolated (p < 0.01). Surprisingly, there was considerable monocyte recruitment in the remote myocardium (approximately 10(4)/mg of myocardium, 5.6-fold increase; p < 0.01), a finding mirrored by macrophage infiltration in the remote myocardium of patients with acute MI. Temporal kinetics of cell recruitment were slower than in the infarct, with peak numbers on day 10 after ischemia. Quantitative polymerase chain reaction showed a robust increase of recruiting adhesion molecules and chemokines in the remote myocardium (e.g., 12-fold increase of monocyte chemoattractant protein-1), although levels were always lower than in the infarct. Finally, matrix metalloproteinase activity was significantly increased in noninfarcted myocardium, suggesting that monocyte recruitment to the remote zone may contribute to post-MI dilation.CONCLUSIONS: This study shed light on the innate inflammatory response in remote myocardium after MI.

AB - OBJECTIVES: The aim of this study was to explore post-myocardial infarction (MI) myocardial inflammation.BACKGROUND: Innate immune cells are centrally involved in infarct healing and are emerging therapeutic targets in cardiovascular disease; however, clinical tools to assess their presence in tissue are scarce. Furthermore, it is currently not known if the nonischemic remote zone recruits monocytes.METHODS: Acute inflammation was followed in mice with coronary ligation by 18-fluorodeoxyglucose ((18)FDG) positron emission tomography/magnetic resonance imaging, fluorescence-activated cell sorting, polymerase chain reaction, and histology.RESULTS: Gd-DTPA-enhanced infarcts showed high (18)FDG uptake on day 5 after MI. Cell depletion and isolation data confirmed that this largely reflected inflammation; CD11b(+) cells had 4-fold higher (18)FDG uptake than the infarct tissue from which they were isolated (p < 0.01). Surprisingly, there was considerable monocyte recruitment in the remote myocardium (approximately 10(4)/mg of myocardium, 5.6-fold increase; p < 0.01), a finding mirrored by macrophage infiltration in the remote myocardium of patients with acute MI. Temporal kinetics of cell recruitment were slower than in the infarct, with peak numbers on day 10 after ischemia. Quantitative polymerase chain reaction showed a robust increase of recruiting adhesion molecules and chemokines in the remote myocardium (e.g., 12-fold increase of monocyte chemoattractant protein-1), although levels were always lower than in the infarct. Finally, matrix metalloproteinase activity was significantly increased in noninfarcted myocardium, suggesting that monocyte recruitment to the remote zone may contribute to post-MI dilation.CONCLUSIONS: This study shed light on the innate inflammatory response in remote myocardium after MI.

KW - Aged

KW - Animals

KW - Case-Control Studies

KW - Female

KW - Fluorodeoxyglucose F18

KW - Humans

KW - Macrophages

KW - Magnetic Resonance Imaging

KW - Male

KW - Matrix Metalloproteinase 2

KW - Matrix Metalloproteinase 9

KW - Mice

KW - Middle Aged

KW - Monocytes

KW - Myocardial Infarction

KW - Myocarditis

KW - Positron-Emission Tomography

KW - Radiopharmaceuticals

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.jacc.2011.08.066

DO - 10.1016/j.jacc.2011.08.066

M3 - Article

VL - 59

SP - 153

EP - 163

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 2

ER -

Lee WW, Marinelli B, van der Laan AM, Sena BF, Gorbatov R, Leuschner F et al. PET/MRI of inflammation in myocardial infarction. Journal of the American College of Cardiology. 2012 Jan 10;59(2):153-163. https://doi.org/10.1016/j.jacc.2011.08.066