Gibb Andrew A, Lazaropoulos Michael P, Elrod John W
From the Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA.
Circ Res. 2020 Jul 17;127(3):427-447. doi: 10.1161/CIRCRESAHA.120.316958. Epub 2020 Jul 16.
Cardiac fibrosis is mediated by the activation of resident cardiac fibroblasts, which differentiate into myofibroblasts in response to injury or stress. Although myofibroblast formation is a physiological response to acute injury, such as myocardial infarction, myofibroblast persistence, as occurs in heart failure, contributes to maladaptive remodeling and progressive functional decline. Although traditional pathways of activation, such as TGFβ (transforming growth factor β) and AngII (angiotensin II), have been well characterized, less understood are the alterations in mitochondrial function and cellular metabolism that are necessary to initiate and sustain myofibroblast formation and function. In this review, we highlight recent reports detailing the mitochondrial and metabolic mechanisms that contribute to myofibroblast differentiation, persistence, and function with the hope of identifying novel therapeutic targets to treat, and potentially reverse, tissue organ fibrosis.
心脏纤维化是由驻留的心脏成纤维细胞激活介导的，这些细胞在受到损伤或应激时会分化为肌成纤维细胞。虽然肌成纤维细胞的形成是对急性损伤（如心肌梗死）的生理反应，但在心力衰竭中出现的肌成纤维细胞持续存在会导致适应性不良的重塑和渐进性的功能衰退。虽然传统的激活途径，如转化生长因子β（TGFβ）和血管紧张素II（AngII），已经得到了很好的描述，但启动和维持肌成纤维细胞形成及功能所必需的线粒体功能和细胞代谢的改变却了解较少。在这篇综述中，我们重点介绍了最近的报告，这些报告详细阐述了有助于肌成纤维细胞分化、持续存在和功能的线粒体及代谢机制，希望能确定新的治疗靶点，以治疗并可能逆转组织器官纤维化。
