In vitro polarized macrophages ameliorate adverse cardiac remodeling in a mouse model of transverse aortic constriction

Bone marrow mononuclear cells (BMNCs) were isolated and subsequently polarized in vitro toward the M2 phenotype using recombinant cytokines (M-csf and Il-4). After confirming the macrophage phenotype by flow cytometry, approximately 3x10^6 cells in 200 ul PBS were administered intravenously on days 7 and 14, which, according to the literature, corresponds to the peak of inflammation and the early stage of resolution after TAC surgery, respectively. At the same time, the control group received only a vehicle (200 ul PBS). To study the transcriptomic profile of polarized macrophages and hearts at different time points and states of the disease, RNA sequencing was used. BMNC and healthy heart tissue were used as control groups, respectively. Most genes associated with anti-inflammatory macrophages, such as Mrc1, Arg1, Retnla, Trem2, Igf1, Fabp5, Gdf15, were up-regulated in macrophages, while in the hearts of mice injected with macrophages, genes responsible for controlled cell division, early transition to fatty acid metabolism, and less fibrosis were over-expressed. All of this indicates that in vitro polarized macrophages obtained using our method can attenuate adverse cardiac remodeling through various mechanisms.