Fig. 4.

Cardiosphere-derived cell (CDC)-extracellular vesicles (EVs) are necessary and sufficient for the upregulation of arginase 1. A: CDC-EV incubation enhanced expression of arginase 1 (Arg1) in macrophages in a dose-dependent manner. B: macrophages cocultured with nSMase2 knockdown (KD) CDCs demonstrated a reduction of Arg1 expression when compared with macrophages cocultured with scrambled CDCs. C: IL4/IL13 (“M2”)-activated macrophages transfected with Arg1 shRNAi demonstrated a reduction in Arg1 expression verifying our in vitro KD model. D: LPS/IFNγ-activated bone marrow-derived macrophages (BMDMs) were transfected with either Arg1 siRNA or a scrambled control before +/− treatment with CDC-EVs. Arg1 expression was enhanced in BMDMs exposed to CDC-EVs but significantly reduced in EV-treated Arg1 KD macrophages (n = 3 biological replicates for each assay, means ± SE, *P < 0.05, Student’s unpaired t test for A–C, one-way ANOVA followed by Tukey’s post-hoc test for D).