J Am Coll Cardiol. 2012 Jan 10;59(2):153-63.

PET/MRI of inflammation in myocardial infarction.

Lee WW, Marinelli B, van der Laan AM, Sena BF, Gorbatov R, Leuschner F, Dutta P, Iwamoto Y, Ueno T, Begieneman MP, Niessen HW, Piek JJ, Vinegoni C, Pittet MJ, Swirski FK, Tawakol A, Di Carli M, Weissleder R, Nahrendorf M.

Source

Center for Systems Biology, Massachusetts General Hospital, Boston, USA.

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.