Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
Departments of Bioengineering and Medicine, University of California San Diego, La Jolla, CA, USA.
Nat Rev Cardiol. 2019 Jun;16(6):361-378. doi: 10.1038/s41569-019-0155-8.
The intact heart undergoes complex and multiscale remodelling processes in response to altered mechanical cues. Remodelling of the myocardium is regulated by a combination of myocyte and non-myocyte responses to mechanosensitive pathways, which can alter gene expression and therefore function in these cells. Cellular mechanotransduction and its downstream effects on gene expression are initially compensatory mechanisms during adaptations to the altered mechanical environment, but under prolonged and abnormal loading conditions, they can become maladaptive, leading to impaired function and cardiac pathologies. In this Review, we summarize mechanoregulated pathways in cardiac myocytes and fibroblasts that lead to altered gene expression and cell remodelling under physiological and pathophysiological conditions. Developments in systems modelling of the networks that regulate gene expression in response to mechanical stimuli should improve integrative understanding of their roles in vivo and help to discover new combinations of drugs and device therapies targeting mechanosignalling in heart disease.
完整的心脏会发生复杂的多尺度重塑过程，以响应改变的机械线索。心肌的重塑受心肌细胞和非心肌细胞对机械敏感途径的反应的组合调控，这些反应可以改变基因表达，从而影响这些细胞的功能。细胞力学转导及其对基因表达的下游效应在适应改变的机械环境时最初是代偿性机制，但在长期和异常的负荷条件下，它们可能变得适应不良，导致功能受损和心脏病变。在这篇综述中，我们总结了心肌细胞和成纤维细胞中受机械调节的途径，这些途径导致在生理和病理生理条件下基因表达和细胞重塑的改变。机械刺激调节基因表达网络的系统建模的发展，应该有助于更好地理解它们在体内的作用，并有助于发现针对心脏疾病中力学信号的药物和器械治疗新组合。
