Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Department of Physiology, Anatomy & Genetics, University of Oxford, Sherrington Building, Sherrington Rd, Oxford OX1 3PT, UK.
Cardiovasc Res. 2022 Jun 22;118(7):1667-1679. doi: 10.1093/cvr/cvab214.
While humans lack sufficient capacity to undergo cardiac regeneration following injury, zebrafish can fully recover from a range of cardiac insults. Over the past two decades, our understanding of the complexities of both the independent and co-ordinated injury responses by multiple cardiac tissues during zebrafish heart regeneration has increased exponentially. Although cardiomyocyte regeneration forms the cornerstone of the reparative process in the injured zebrafish heart, recent studies have shown that this is dependent on prior neovascularization and lymphangiogenesis, which in turn require epicardial, endocardial, and inflammatory cell signalling within an extracellular milieu that is optimized for regeneration. Indeed, it is the amalgamation of multiple regenerative systems and gene regulatory patterns that drives the much-heralded success of the adult zebrafish response to cardiac injury. Increasing evidence supports the emerging paradigm that developmental transcriptional programmes are re-activated during adult tissue regeneration, including in the heart, and the zebrafish represents an optimal model organism to explore this concept. In this review, we summarize recent advances from the zebrafish cardiovascular research community with novel insight into the mechanisms associated with endogenous cardiovascular repair and regeneration, which may be of benefit to inform future strategies for patients with cardiovascular disease.
虽然人类在受伤后缺乏足够的心脏再生能力，但斑马鱼可以从各种心脏损伤中完全恢复。在过去的二十年中，我们对斑马鱼心脏再生过程中多种心脏组织的独立和协调损伤反应的复杂性的理解呈指数级增长。虽然心肌细胞再生构成了受伤斑马鱼心脏修复过程的基石，但最近的研究表明，这依赖于先前的血管生成和淋巴管生成，而血管生成和淋巴管生成又需要心外膜、心内膜和炎症细胞信号在有利于再生的细胞外环境中进行协调。事实上，正是多种再生系统和基因调控模式的融合，推动了成年斑马鱼对心脏损伤反应的巨大成功。越来越多的证据支持这样一种新兴观点，即在成年组织再生过程中，包括心脏在内，发育转录程序被重新激活，而斑马鱼则是探索这一概念的理想模式生物。在这篇综述中，我们总结了来自斑马鱼心血管研究界的最新进展，为内源性心血管修复和再生相关机制提供了新的见解，这可能有助于为心血管疾病患者提供未来的治疗策略。
