Zebrafish Models in Therapeutic Research of Cardiac Conduction Disease.

Zebrafish Models in Therapeutic Research of Cardiac Conduction Disease.
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DOI:
10.3389/fcell.2021.731402
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发表时间:
2021
影响因子:
5.5
通讯作者:
Ren J
Ren J
中科院分区:
生物学2区
文献类型:
--
作者:
Gao R;Ren J

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先天性异常或疾病引起的心脏传导系统(CCS)功能障碍可引起心脏传导疾病(CCD),导致心律紊乱,导致晕厥甚至心源性猝死。对包括起搏器心肌细胞(CMs)、房室结(AVN)和心室传导系统(VCS)在内的CCS组成部分的发展的深入了解,可以揭示CCD的病理和分子机制,为生成人类多能干细胞(hPSC)衍生的CCS细胞提供方法,从而改善对这一潜在危及生命的心脏疾病的治疗。然而,控制CCS发展的细胞和分子机制仍然难以捉摸。斑马鱼具有体外受精、胚胎光学透明以及即使在发育过程中存在严重的心血管缺陷也能存活等独特特征,因此成为研究CCS组件早期发育的有价值的脊椎动物模型。在这篇综述中,我们重点介绍了如何利用斑马鱼来解剖CCS发育的细胞和分子机制,以及如何将斑马鱼中发现的进化保守的发育机制应用于指导hscs衍生的CCS细胞的产生,从而提供潜在的治疗策略,可能有助于更好地治疗CCD患者。
Malfunction in the cardiac conduction system (CCS) due to congenital anomalies or diseases can cause cardiac conduction disease (CCD), which results in disturbances in cardiac rhythm, leading to syncope and even sudden cardiac death. Insights into development of the CCS components, including pacemaker cardiomyocytes (CMs), atrioventricular node (AVN) and the ventricular conduction system (VCS), can shed light on the pathological and molecular mechanisms underlying CCD, provide approaches for generating human pluripotent stem cell (hPSC)-derived CCS cells, and thus improve therapeutic treatment for such a potentially life-threatening disorder of the heart. However, the cellular and molecular mechanisms controlling CCS development remain elusive. The zebrafish has become a valuable vertebrate model to investigate early development of CCS components because of its unique features such as external fertilization, embryonic optical transparency and the ability to survive even with severe cardiovascular defects during development. In this review, we highlight how the zebrafish has been utilized to dissect the cellular and molecular mechanisms of CCS development, and how the evolutionarily conserved developmental mechanisms discovered in zebrafish could be applied to directing the creation of hPSC-derived CCS cells, therefore providing potential therapeutic strategies that may contribute to better treatment for CCD patients.
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