先天性心脏病中心肌细胞的增殖与再生

Cardiomyocyte proliferation and regeneration in congenital heart disease.

作者信息

Liang Jialiang, He Xingyu, Wang Yigang

机构信息

Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.

出版信息

Pediatr Discov. 2024 Sep;2(3). doi: 10.1002/pdi3.2501. Epub 2024 Aug 12.

Abstract

Despite advances in prenatal screening and a notable decrease in mortality rates, congenital heart disease (CHD) remains the most prevalent congenital disorder in newborns globally. Current therapeutic surgical approaches face challenges due to the significant rise in complications and disabilities. Emerging cardiac regenerative therapies offer promising adjuncts for CHD treatment. One novel avenue involves investigating methods to stimulate cardiomyocyte proliferation. However, the mechanism of altered cardiomyocyte proliferation in CHD is not fully understood, and there are few feasible approaches to stimulate cardiomyocyte cell cycling for optimal healing in CHD patients. In this review, we explore recent progress in understanding genetic and epigenetic mechanisms underlying defective cardiomyocyte proliferation in CHD from development through birth. Targeting cell cycle pathways shows promise for enhancing cardiomyocyte cytokinesis, division, and regeneration to repair heart defects. Advancements in human disease modeling techniques, CRISPR-based genome and epigenome editing, and next-generation sequencing technologies will expedite the exploration of abnormal machinery governing cardiomyocyte differentiation, proliferation, and maturation across diverse genetic backgrounds of CHD. Ongoing studies on screening drugs that regulate cell cycling are poised to translate this nascent technology of enhancing cardiomyocyte proliferation into a new therapeutic paradigm for CHD surgical interventions.

摘要

尽管产前筛查取得了进展,死亡率显著下降,但先天性心脏病(CHD)仍然是全球新生儿中最常见的先天性疾病。由于并发症和残疾率大幅上升,目前的治疗性手术方法面临挑战。新兴的心脏再生疗法为CHD治疗提供了有前景的辅助手段。一种新途径是研究刺激心肌细胞增殖的方法。然而,CHD中心肌细胞增殖改变的机制尚未完全了解,并且几乎没有可行的方法来刺激心肌细胞周期循环以实现CHD患者的最佳愈合。在这篇综述中,我们探讨了从发育到出生过程中,在理解CHD中心肌细胞增殖缺陷的遗传和表观遗传机制方面的最新进展。靶向细胞周期途径有望增强心肌细胞的胞质分裂、分裂和再生,以修复心脏缺陷。人类疾病建模技术、基于CRISPR的基因组和表观基因组编辑以及下一代测序技术的进步将加速探索在CHD的不同遗传背景下控制心肌细胞分化、增殖和成熟的异常机制。正在进行的筛选调节细胞周期的药物的研究有望将这种增强心肌细胞增殖的新兴技术转化为CHD手术干预的新治疗模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c40a/12118177/c1f74b58cf3a/PDI3-2-e2501-g003.jpg

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