Abstract 9018: Serial in vivo Imaging Reveals a Key Function for Splenic Monocytes in Infarct Healing
The splenic monocyte reservoir contributes substantially to acute inflammation, and these cells participate centrally in tissue repair after myocardial infarction (MI). We here investigated the relevance of the splenic reservoir monocytes for infarct healing and left ventricular remodeling.
Methods: Mice received coronary artery ligation and splenectomy either on the day of MI or 3 days later, and were then followed by cardiac MRI (day 1 and 21 after MI, figure). On day 5 after MI, they underwent three-channel fluorescent molecular tomography (FMT-CT) to quantify uptake of a monocyte/macrophage-targeted fluorescent nanoparticle and a fluorescently labeled integrin probe, and activation of a protease sensor in the heart. Mice with coronary ligation but without splenectomy served as controls.
Results: Removal of the spleen reduced accumulation of nanoparticles, indicating reduced monocyte/macrophage phagocytic activity in the infarct. Proteolytic potential and integrin expression were reduced as well, independent of splenectomy time (p<0.05 versus MI only, figure). Splenectomy at either time-point significantly impaired left ventricular ejection fraction on MRI (MI only, 50±6%; MI and immediate splenectomy, 32±4%; MI and splenectomy 3 days later, 36±4%; p<0.05 versus MI only) and resulted in a thinner scar (530±50μ m, 320±20μ m, 370±20μ m, p<0.05 versus MI only). Ex vivo analysis in additional cohorts corroborated in vivo imaging data.
Conclusion: Removal of the spleen reduced monocyte-mediated healing biomarkers and resulted in infarct expansion and accelerated left ventricular remodeling. Thus, spleen-derived macrophages likely promote healing of the infarcting myocardium.
- © 2011 by American Heart Association, Inc.