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心脏发育的生理学:从基因到信号传导再到治疗策略

Physiology of Cardiac Development: From Genetics to Signaling to Therapeutic Strategies.

作者信息

Sun Cheng, Kontaridis Maria I

机构信息

Department of Medicine, Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.

出版信息

Curr Opin Physiol. 2018 Feb;1:123-139. doi: 10.1016/j.cophys.2017.09.002. Epub 2017 Dec 13.

Abstract

The heart is one of the first organs to form and function during embryonic development. It is comprised of multiple cell lineages, each integral for proper cardiac development, and include cardiomyocytes, endothelial cells, epicardial cells and neural crest cells. The molecular mechanisms regulating cardiac development and morphogenesis are dependent on signaling crosstalk between multiple lineages through paracrine interactions, cell-ECM interactions, and cell-cell interactions, which together, help facilitate survival, growth, proliferation, differentiation and migration of cardiac tissue. Aberrant regulation of any of these processes can induce developmental disorders and pathological phenotypes. Here, we will discuss each of these processes, the genetic factors that contribute to each step of cardiac development, as well as the current and future therapeutic targets and mechanisms of heart development and disease. Understanding the complex interactions that regulate cardiac development, proliferation and differentiation is not only vital to understanding the causes of congenital heart defects, but to also finding new therapeutics that can treat both pediatric and adult cardiac disease in the near future.

摘要

心脏是胚胎发育过程中最早形成并开始发挥功能的器官之一。它由多种细胞谱系组成,每种细胞谱系对于心脏的正常发育都不可或缺,包括心肌细胞、内皮细胞、心外膜细胞和神经嵴细胞。调节心脏发育和形态发生的分子机制依赖于多种谱系之间通过旁分泌相互作用、细胞与细胞外基质相互作用以及细胞与细胞相互作用进行的信号串扰,这些相互作用共同促进心脏组织的存活、生长、增殖、分化和迁移。这些过程中任何一个的异常调节都可能诱发发育障碍和病理表型。在此,我们将讨论这些过程中的每一个、促成心脏发育各个步骤的遗传因素,以及心脏发育和疾病的当前及未来治疗靶点与机制。了解调节心脏发育、增殖和分化的复杂相互作用不仅对于理解先天性心脏缺陷的成因至关重要,对于在不久的将来找到能够治疗儿科和成人心脏疾病的新疗法也至关重要。

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