Cardiomyocyte-Derived Vesicles Are Taken Up into Fibroblasts, Leading to Profibrotic Transcriptome Changes
(A) Setup to evaluate a potential vesicle-mediated crosstalk between hypoxic cardiomyocytes and fibroblasts. (B–E) Expression levels of fibrosis-related genes Col1a1 (B), Col3a1 (C), Ctgf (D), and MMP2 (E) in fibroblasts after culture with hypoxic or normoxic conditioned medium. (F–I) Stepwise depletion of large vesicles (− lEVs) or all extracellular vesicles (−all EVs) out of the conditioned medium abolished the profibrotic phenotype: (F) Col1a1; (G) Col3a1; (H) Ctgf; and (I) MMP2. Data are presented as mean ± SEM. n = 4–5 independent experiments. *p ≤ 0.05; **p ≤ 0.01; ns, not significant; Student’s t test. FC, fold change to normoxic control.