Putting the Heat on Cardiac Fibrosis: Hsp20 Regulates Myocyte-To-Fibroblast Crosstalk.
Putting the Heat on Cardiac Fibrosis: Hsp20 Regulates Myocyte-To-Fibroblast Crosstalk.
复制标题
治疗心脏纤维化：Hsp20 调节心肌细胞与成纤维细胞的串扰。
DOI：
10.1016/j.jacbts.2019.03.007
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
McKinsey,TimothyA
中科院分区：
文献类型：
--
作者：
Major,JenniferL;McKinsey,TimothyA
纤维化是由组织损伤或压力触发的伤口愈合过程。心脏纤维化与几种形式的心力衰竭（HF）的不良结局相关，包括射血分数降低的HF、射血分数保持的HF和遗传驱动的心肌病（1，2）。尽管伴随纤维化反应的细胞外基质（ECM）沉积增加可能会急性稳定心肌损伤的焦点区域，但过度、弥漫或慢性纤维化激活可能对长期心脏功能和患者生存有害。例如，纤维化可以增加心肌的被动刚度，这有助于舒张功能障碍（3，4），并可以破坏心脏中的电传导，这会导致心律失常和心脏性猝死（5）。不幸的是，尽管纤维化在心功能不全中的作用被广泛接受，但不存在针对心脏的靶向抗纤维化药物。因此，了解驱动心脏纤维化的基本机制是至关重要的，以便能够发现阻止这种致病过程的新方法。心脏中的常驻成纤维细胞是心脏纤维化的主要贡献者（6，7）。响应于应激，这些细胞经历细胞状态转变以成为活化的成纤维细胞，有时称为肌成纤维细胞，其产生高水平的ECM。来自死亡的肌细胞、白细胞、血管细胞和驻留的成纤维细胞本身的炎症线索历来被视为心脏中成纤维细胞活化的主要驱动因素。然而，越来越多的证据支持肌细胞源性分泌因子在控制心脏成纤维细胞活化中的作用（8，9）。在本期
Fibrosis is a wound-healing process that is triggered by tissue injury or stress. Cardiac fibrosis is associated with adverse outcomes in several forms of heart failure (HF), including HF with reduced ejection fraction, HF with preserved ejection fraction, and genetically driven cardiomyopathies (1, 2). Although the increased extracellular matrix (ECM) deposition that accompanies fibrotic responses may acutely serve to stabilize a focal area of myocardial damage, excessive, diffuse, or chronic activation of fibrosis can be deleterious to long-term cardiac function and patient survival. For example, fibrosis can increase the passive stiffness of the myocardium, which contributes to diastolic dysfunction (3, 4), and can disrupt electrical conduction in the heart, which causes arrhythmias and sudden cardiac death (5). Unfortunately, despite the well-accepted roles of fibrosis in cardiac dysfunction, no targeted antifibrotic drugs for the heart exist. Thus, it is crucial to understand the fundamental mechanisms that drive cardiac fibrosis so that novel approaches to thwart this pathogenic process can be discovered. Resident fibroblasts in the heart are major contributors to cardiac fibrosis (6, 7). In response to stress, these cells undergo a cell state transition to become activated fibroblasts, sometimes referred to as myofibroblasts, which produce high levels of ECM. Inflammatory cues from dead myocytes, leukocytes, vascular cells, and resident fibroblasts themselves have historically been viewed as the major drivers of fibroblast activation in the heart. However, there is a growing body of evidence to support a role for myocyte-derived secreted factors in the control of the cardiac fibroblast activation (8, 9). In this issue of