PET/MRI of inflammation in myocardial infarction.
OBJECTIVE
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.
Center for Systems Biology, Massachusetts General Hospital, Boston, USA.
Won Woo
WW
Lee
Brett
B
Marinelli
Anja M
AM
van der Laan
Brena F
BF
Sena
Rostic
R
Gorbatov
Florian
F
Leuschner
Partha
P
Dutta
Yoshiko
Y
Iwamoto
Takuya
T
Ueno
Mark P V
MP
Begieneman
Hans W M
HW
Niessen
Jan J
JJ
Piek
Claudio
C
Vinegoni
Mikael J
MJ
Pittet
Filip K
FK
Swirski
Ahmed
A
Tawakol
Marcelo
M
Di Carli
Ralph
R
Weissleder
Matthias
M
Nahrendorf
D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000201:enzymology / Q000276:immunology; D009205:Myocarditis / Q000000981:diagnostic imaging* / Q000201:enzymology / Q000276:immunology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse