Pathophysiology and therapeutic potential of cardiac fibrosis.
Pathophysiology and therapeutic potential of cardiac fibrosis.
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DOI：
10.1186/s41232-017-0046-5
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发表时间：
2017
影响因子：
8.1
通讯作者：
Komuro I
中科院分区：
文献类型：
--
作者：
Hara H;Takeda N;Komuro I
对心肌损伤的炎症和纤维化反应对心脏修复至关重要；然而，这些反应往往导致广泛的纤维化重塑以及收缩功能受损。近期的报道表明，这种急性期反应为内源性心脏再生提供了有利环境，而内源性心脏再生主要由预先存在的心肌细胞（CMs）分裂所驱动。哺乳动物中现有的心肌细胞在严重心脏损伤后可重新获得增殖活性，并且生理和/或病理环境中除心肌细胞外的因素，如缺氧、血管生成以及浸润巨噬细胞的极性，据报道可调节其复制。就心肌中的细胞数量而言，心脏成纤维细胞是数量最多的细胞群体，它们在心肌细胞的增殖和保护中起着关键作用。功能性心肌细胞的体内直接重编程已在心脏再生中得到研究。目前，促进这些心肌细胞再生和保护的生长因子、转录因子、微小RNA和小分子也得到了积极研究。在此，我们总结并讨论了当前关于心脏炎症和纤维化以及心脏再生和保护之间关系的研究，这将有助于制定治疗和预防晚期心力衰竭的治疗策略。
Inflammatory and fibrotic responses to myocardial damage are essential for cardiac repair; however, these responses often result in extensive fibrotic remodeling with impaired systolic function. Recent reports have suggested that such acute phase responses provide a favorable environment for endogenous cardiac regeneration, which is mainly driven by the division of pre-existing cardiomyocytes (CMs). Existing CMs in mammals can re-acquire proliferative activity after substantial cardiac damage, and elements other than CMs in the physiological and/or pathological environment, such as hypoxia, angiogenesis, and the polarity of infiltrating macrophages, have been reported to regulate replication. Cardiac fibroblasts comprise the largest cell population in terms of cell number in the myocardium, and they play crucial roles in the proliferation and protection of CMs. The in vivo direct reprogramming of functional CMs has been investigated in cardiac regeneration. Currently, growth factors, transcription factors, microRNAs, and small molecules promoting the regeneration and protection of these CMs have also been actively researched. Here, we summarize and discuss current studies on the relationship between cardiac inflammation and fibrosis, and cardiac regeneration and protection, which would be useful for the development of therapeutic strategies to treat and prevent advanced heart failure.