Paracrine signaling from different fibroblast phenotypes differentially regulates adult cardiomyocyte viability, volume, and calcium handling, with TGF-β playing a crucial role in this crosstalk.
Fibroblasts and cardiomyocytes engage in bi-directional crosstalk mediated by soluble factors like TGF-β, which differentially affects cardiomyocyte function and hypertrophy depending on the fibroblast phenotype.
AIMS: Crosstalk between cardiomyocytes and fibroblasts in physiological conditions and during disease remains poorly defined. Previous studies have shown that fibroblasts and myocytes interact via paracrine communication, but several experimental confounding factors, including the use of immature myocytes and the induction of alpha-smooth muscle actin (α-SMA) expression in fibroblasts by prolonged culture, have hindered our understanding of this phenomenon. We hypothesize that fibroblasts and myofibroblasts differentially affect cardiomyocytes viability, volume, and Ca(2+) handling via soluble mediators. More specifically here: (i) we compare the effects of freshly isolated fibroblasts and cultured fibroblasts from normal rat hearts on adult cardiomyocytes; (ii) we compare the effects of (freshly isolated) normal fibroblasts and myofibroblasts from pressure-overloaded hearts; and (iii) we study the contribution of TGF-β and the importance of the crosstalk between the two cell types. METHODS AND RESULTS: We used co-culture methods and conditioned medium to investigate paracrine interaction between fibroblasts and cardiomyocytes. All fibroblast types reduce cardiomyocyte viability and increase cardiomyocyte volume but α-SMA-negative fibroblasts increase cardiomyocyte Ca(2+) transient amplitude, whereas cultured fibroblasts and myofibroblasts from pressure-overloaded hearts decrease Ca(2+) transient amplitude. In turn, cardiomyocytes release soluble mediators that affect fibroblast proliferation. Using SB431542 to block TGF-β type 1 receptors, we determined that TGF-β directly causes cardiomyocyte hypertrophy and participates in bi-directional regulatory signalling between fibroblasts and cardiomyocytes. CONCLUSIONS: Fibroblasts have different roles during physiology and disease in regulating myocardial function via soluble mediators. A crosstalk between fibroblasts and cardiomyocytes, controlled by TGF-β, is crucial in this interaction.
Cartledge et al. (Mon,) conducted a other in Cardiac fibroblast and cardiomyocyte crosstalk. Fibroblast conditioned medium and co-culture vs. Different fibroblast phenotypes was evaluated on Cardiomyocyte viability, volume, and Ca(2+) transient amplitude. Paracrine signaling from different fibroblast phenotypes differentially regulates adult cardiomyocyte viability, volume, and calcium handling, with TGF-β playing a crucial role in this crosstalk.
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