Activation of cardiac macrophages, endothelial cells and fibroblasts in experimental autoimmune myocarditis

Abstract Background/Introduction Inflammation of cardiac tissue, termed myocarditis, is a common cause dilated cardiomyopathy associated with abnormal tissue remodeling, stiffening ventricles and heart failure. Experimental autoimmune myocarditis (EAM) represents CD4+ T cell-dependent animal model acute followed by development cardiomyopathy, fibrosis systolic dysfunction. Purpose The aim the study was to investigate role macrophages, endothelial cells fibroblasts in post-inflammatory mouse EAM. Methods EAM induced BALB/c mice immunization alpha myosin heavy chain complete Freund's adjuvant. Reporter expressing EGFP under collagen type I promoter (Coll-EGFP), transgenic αSMA-TK ganciclovir-inducible ablation proliferating myofibroblasts Rosa26-YFP/LysM-Cre Rosa26-YFP/LysM-Cre/Tgfbr2 fl/fl YFP expression Tgfbr2 deletion myeloid cell population were used this study. Cardiac macrophages sorted using BD FACSAria™ II Cell Sorter analyzed for genome transcriptomics RNA sequencing. Echocardiography performed on Vevo 2100 Imaging System. measured as percentage fibrotic area Trichrome Massons's staining hydroxyproline assay. hypertrophy means cross-sectional cardiomyocyte area. Monocytes endobcells FACSCanto™ flow cytometry. Results response (d21 EAM) showed activation immune processes (mainly chemokine production such Ccl6, Ccl9, Cxcl2, Cxcl3, Cxcl5, Cxcl9, Cxcl13), cytoskeletal re-organization (Cxadr, F11r, Gdpd2, Krt8, Krt19, Ptk2b, Rac2, Rhov, Rnd1, S100a9, Spire2, Was) upregulation genes involved extracellular matrix turnover (Bmp7, Kng2, Lgals3, Cthrc1, Cela1, Spn) including collagens. Ablation (between d21–40 resulted markedly reduced weight hypertrophy, attenuated related (Acta1, Actc1, Bnp, Cfl2, Pdlim5), improved stroke volume, ejection fraction output but did not prevent at d40 Analysis monocytes indicated excessive these d21. pointed out TGF-β-dependent cytokines (Ifn, Il23a, Il10, Il12b, Cxcl1, Tnf) theirs receptors (Cxcr1, Ccr4) d21 Conclusions Acute activates proinflammatory profibrotic responses resident cells. Our data suggest that play particularly important Targeting might therefore represent novel therapeutic strategy inflammatory disease. Funding Acknowledgement Type funding sources: Public grant(s) – National budget only. Main source(s): Science Centre (Poland)