Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg∙Bad Krozingen, 79110 Freiburg im Breisgau, Germany.
Medical Center and Faculty of Medicine, University of Freiburg, 79110 Freiburg im Breisgau, Germany.
Int J Mol Sci. 2023 Jun 30;24(13):10961. doi: 10.3390/ijms241310961.
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., in the atria (compared to the ventricles), in the right atrium (compared to the left atrium), and in the left atrium (compared to the right atrium), as well as and in ventricles (compared to the atria). Furthermore, 15 MSC genes are differentially expressed in cardiac disease, out of which (lower expressed in heart failure compared to donor tissue) and (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.
心脏细胞的机械环境会随着每次心跳和各种心脏疾病的发生而发生变化。细胞通过专门的机械感受器感知和响应机械线索，从而启动适应性信号级联反应。为了揭示与心脏疾病相关的机械转导的新候选物，我们研究了人类心脏中的机械敏感离子通道（MSC），以了解其与心室和疾病相关的 mRNA 表达。基于对 RNA 测序研究的荟萃分析，我们比较了来自移植供体心脏（无心脏病）和窦性节律患者（潜在疾病：心力衰竭、冠状动脉疾病、心脏瓣膜疾病）或心房颤动患者的人类心房和心室组织样本中 MSC 的 mRNA 表达水平。我们的研究结果表明，许多 MSC 基因在心房（与心室相比）、右心房（与左心房相比）和左心房（与右心房相比）中呈 chamber-preferentially 表达，以及在心室（与心房相比）中呈 chamber-preferentially 表达。此外，在心脏疾病中，有 15 个 MSC 基因表达存在差异，其中（在心力衰竭中表达低于供体组织）和（在心房颤动中表达低于窦性节律）差异超过两倍，表明可能具有功能相关性。因此，我们提供了来自不同心脏疾病患者的四个心腔中心脏 MSC mRNA 表达的概述。我们认为，观察到的 MSC mRNA 表达差异可能可以识别与各自疾病中改变的机械转导相关的候选物。
