Wilsbacher Lisa, McNally Elizabeth M
Department of Medicine, Center for Genetic Medicine, and Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611; email:
Annu Rev Pathol. 2016 May 23;11:395-419. doi: 10.1146/annurev-pathol-012615-044336. Epub 2016 Feb 24.
Cardiac developmental disorders represent the most common of human birth defects, and anomalies in cardiomyocyte proliferation drive many of these disorders. This review highlights the molecular mechanisms of prenatal cardiac growth. Trabeculation represents the initial ventricular growth phase and is necessary for embryonic survival. Later in development, the bulk of the ventricular wall derives from the compaction process, yet the arrest of this process can still be compatible with life. Cardiomyocyte proliferation and growth form the basis of both trabeculation and compaction, and mouse models indicate that cardiomyocyte interactions with the surrounding environment are critical for these proliferative processes. The human genetics of left ventricular noncompaction cardiomyopathy suggest that cardiomyocyte cell-autonomous mechanisms contribute to the compaction process. Understanding the determinants of prenatal or early postnatal cardiomyocyte proliferation and growth provides critical information that identifies risk factors for cardiovascular disease, including heart failure and its associated complications of arrhythmias and thromboembolic events.
心脏发育障碍是人类最常见的出生缺陷，心肌细胞增殖异常是导致许多此类障碍的原因。本综述重点介绍产前心脏生长的分子机制。小梁形成代表心室生长的初始阶段，是胚胎存活所必需的。在发育后期，心室壁的大部分来自致密化过程，但该过程的停滞仍可与生命相容。心肌细胞的增殖和生长是小梁形成和致密化的基础，小鼠模型表明心肌细胞与周围环境的相互作用对这些增殖过程至关重要。左心室致密化不全心肌病的人类遗传学研究表明，心肌细胞的自主机制有助于致密化过程。了解产前或出生后早期心肌细胞增殖和生长的决定因素，可为识别心血管疾病的风险因素提供关键信息，这些疾病包括心力衰竭及其相关的心律失常和血栓栓塞事件并发症。
