TREK-1 knock-down in human atrial fibroblasts leads to a myofibroblastic phenotype: a role in phenoconversion and over-view of mechano-sensitive channel mRNA expression in cardiac diseases

Cardiac cell mechanical environment changes on a beat-by-beat basis and also in the course of various cardiac diseases. Cells sense and adapt to such mechanical cues via specialized mechano-sensors mediating adaptive signaling cascades. Here, we report TREK-1 mRNA expression and activity in human atrial fibroblasts and reveal a cross talk between TREK-1 and fibroblast phenoconversion. With the aim to reveal additional candidates underlying mechano-transduction relevant to cardiac diseases, we investigated mechano-sensitive ion channels (MSC) mRNA expression in diseased and non-diseased human hearts. Our results showed higher TREK-1 expression and activity in fibroblasts compared to myofibroblasts and we found that TREK-1 down-regulation leads a more myofibroblastic phenotype suggesting a role for this mechano-sensor in phenoconversion. In addition, TREK-1 is preferentially expressed in the left atrium compared to the right one and its expression is not significantly changed when fibroblasts from patients in sinus rhythm vs. sustained atrial fibrillation are compared. At the whole-heart level, numerous MSC were differentially expressed between atrial and ventricular or between non-diseased and diseased tissue samples. Thus, we identify atrial fibroblast-specific TREK-1 expression and activity and reveal a role of TREK-1 in atrial fibroblast pheno-conversion. We also provide a comprehensive overview of cardiac MSC mRNA expression in atrial and ventricular tissue from diseased and non-diseased patients, identifying potential novel candidates underlying mechanotransduction in cardiac diseases. ### Competing Interest Statement All authors declare no conflict of interest. SR was employed by Amgen Inc., at the time of submission of the manuscript. The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.