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Functional crosstalk between cardiac fibroblasts and adult cardiomyocytes by soluble mediators.

Abstract：

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.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Cartledge JE,Kane C,Dias P,Tesfom M,Clarke L,Mckee B,Al Ayoubi S,Chester A,Yacoub MH,Camelliti P,Terracciano CM

doi

10.1093/cvr/cvu264

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

260-70

issue

eissn

0008-6363

issn

1755-3245

pii

cvu264

journal_volume

105

pub_type

杂志文章

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Functional crosstalk between cardiac fibroblasts and adult cardiomyocytes by soluble mediators.