In heart failure, cardiac fibrosis is the result of an adverse remodeling process. Collagen is continuously synthesized in the myocardium in an ongoing attempt of the heart to repair itself. The resulting collagen depositions act counterproductively, causing diastolic dysfunction and disturbing electrical conduction. Efforts to treat cardiac fibrosis specifically have not been successful and the molecular etiology is only partially understood. The differentiation of quiescent cardiac fibroblasts to extracellular matrix-depositing myofibroblasts is a hallmark of cardiac fibrosis and a key aspect of the adverse remodeling process. This conversion is induced by a complex interplay of biochemical signals and mechanical stimuli. Tissue-engineered 3D models to study cardiac fibroblast behavior in vitro indicate that cyclic strain can activate a myofibroblast phenotype. This raises the question how fibroblast quiescence is maintained in the healthy myocardium, despite continuous stimulation of ultimately profibrotic mechanotransductive pathways. In this review, we will discuss the convergence of biochemical and mechanical differentiation signals of myofibroblasts, and hypothesize how these affect this paradoxical quiescence.

中文翻译：

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先进的体外建模研究机械诱导的心脏纤维化的悖论

在心力衰竭中，心脏纤维化是不良重塑过程的结果。胶原蛋白在心肌中不断合成，心脏不断尝试自我修复。由此产生的胶原蛋白沉积会适得其反，导致舒张功能障碍和干扰电传导。专门治疗心脏纤维化的努力尚未成功，分子病因学仅部分了解。静止的心脏成纤维细胞分化为细胞外基质沉积的肌成纤维细胞是心脏纤维化的标志，也是不良重塑过程的一个关键方面。这种转化是由生化信号和机械刺激的复杂相互作用引起的。用于体外研究心脏成纤维细胞行为的组织工程 3D 模型表明循环应变可以激活肌成纤维细胞表型。这提出了一个问题，尽管最终促纤维化机械转导通路不断受到刺激，但成纤维细胞如何在健康心肌中保持静止。在这篇综述中，我们将讨论肌成纤维细胞的生化和机械分化信号的融合，并假设这些信号如何影响这种矛盾的静止。