Modulation of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair

Tamar Harel-Adar, Tamar Ben Mordechai, Yoram Amsalem, Micha S. Feinberg, Jonathan Leor, Smadar Cohen

Research output: Contribution to journalArticlepeer-review

Abstract

Herein we investigated a new strategy for the modulation of cardiac macrophages to a reparative state, at a predetermined time after myocardial infarction (MI), in aim to promote resolution of inflammation and elicit infarct repair. The strategy employed intravenous injections of phosphatidylserine (PS)-presenting liposomes, mimicking the anti-inflammatory effects of apoptotic cells. Following PS-liposome uptake by macrophages in vitro and in vivo, the cells secreted high levels of anti-inflammatory cytokines [transforming growth factor β (TGFβ) and interleukin 10 (IL-10)] and upregulated the expression of the mannose receptor - CD206, concomitant with downregulation of proinflammatory markers, such as tumor necrosis factor α (TNFα) and the surface marker CD86. In a rat model of acute MI, targeting of PS-presenting liposomes to infarct macrophages after injection via the femoral vein was demonstrated by magnetic resonance imaging (MRI). The treatment promoted angiogenesis, the preservation of small scars, and prevented ventricular dilatation and remodeling. This strategy represents a unique and accessible approach for myocardial infarct repair.

Original languageEnglish
Pages (from-to)1827-1832
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number5
DOIs
StatePublished - 1 Feb 2011

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