Macrophages play an important role in inflammation and cardiac remodeling in response to myocardial infarction (MI). Earlier shift of inflammtory M1 macrophages to reparative M2 macrophages has demonstrated significant improvements in MI wound modeling and cardiac function. Here, we reported that TSLP could promote M1 to M2 macrophage polarization, and AngII skewed the macrophage phenotype towards M2 by inducing TSLP expression in vitro. Meanwhile, AngII could inhibit the expression of MMP2 and MMP9 in macrophages, which are engaged in ECM degradation and cardiac remodeling. In post-MI mice, TSLP expression were up-regulated in cardiac tissue and serum, probably induced by renin-angiotensin system activation and AngII level up-regulation following MI. Our study mapped the continuum of changes that occured in cardiac macrophages over the first week of MI, and found that rTSLP treatment promoted earlier phenotype shift of M1 to M2 macrophages, improving cardiac healing and ventricular function recovery. Taken together, this work identified a very promising therapeutic opportunity to manage macrophage phenotype and enhance resolution of inflammation in the post-MI heart.
Keywords: Cardiac remodeling; Macrophage polarization; Myocardial infarction; TSLP.
Copyright © 2019 Elsevier Inc. All rights reserved.