Meta-Analysis of Mechano-Sensitive Ion Channels in Human Hearts: Chamber- and Disease-Preferential mRNA Expression

oleh: Elisa Darkow, Dilmurat Yusuf, Sridharan Rajamani, Rolf Backofen, Peter Kohl, Ursula Ravens, Rémi Peyronnet

Format: Article
Diterbitkan: MDPI AG 2023-06-01

Deskripsi

The cardiac cell mechanical environment changes on a beat-by-beat basis as well as in the course of various cardiac diseases. Cells sense and respond to mechanical cues via specialized mechano-sensors initiating adaptive signaling cascades. With the aim of revealing new candidates underlying mechano-transduction relevant to cardiac diseases, we investigated mechano-sensitive ion channels (MSC) in human hearts for their chamber- and disease-preferential mRNA expression. Based on a meta-analysis of RNA sequencing studies, we compared the mRNA expression levels of MSC in human atrial and ventricular tissue samples from transplant donor hearts (no cardiac disease), and from patients in sinus rhythm (underlying diseases: heart failure, coronary artery disease, heart valve disease) or with atrial fibrillation. Our results suggest that a number of MSC genes are expressed chamber preferentially, e.g., <i>CHRNE</i> in the atria (compared to the ventricles), <i>TRPV4</i> in the right atrium (compared to the left atrium), <i>CACNA1B</i> and <i>KCNMB1</i> in the left atrium (compared to the right atrium), as well as <i>KCNK2</i> and <i>KCNJ2</i> in ventricles (compared to the atria). Furthermore, 15 MSC genes are differentially expressed in cardiac disease, out of which <i>SCN9A</i> (lower expressed in heart failure compared to donor tissue) and <i>KCNQ5</i> (lower expressed in atrial fibrillation compared to sinus rhythm) show a more than twofold difference, indicative of possible functional relevance. Thus, we provide an overview of cardiac MSC mRNA expression in the four cardiac chambers from patients with different cardiac diseases. We suggest that the observed differences in MSC mRNA expression may identify candidates involved in altered mechano-transduction in the respective diseases.