Lin Wen, Li Deqiang
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 10591, USA.
Pediatr Cardiol. 2018 Jun;39(5):1042-1051. doi: 10.1007/s00246-018-1859-y. Epub 2018 Mar 13.
Ventricular myocardial development is a well-orchestrated process involving different cardiac structures, multiple signal pathways, and myriad proteins. Dysregulation of this important developmental event can result in cardiomyopathies, such as left ventricle non-compaction, which affect the pediatric population and the adults. Human and mouse studies have shed light upon the etiology of some cardiomyopathy cases and highlighted the contribution of both genetic and environmental factors. However, the regulation of ventricular myocardial development remains incompletely understood. Zinc is an essential trace metal with structural, enzymatic, and signaling function. Perturbation of zinc homeostasis has resulted in developmental and physiological defects including cardiomyopathy. In this review, we summarize several mechanisms by which zinc and zinc transporters can impact the regulation of ventricular myocardial development. Based on our review, we propose that zinc deficiency and mutations of zinc transporters may underlie some cardiomyopathy cases especially those involving ventricular myocardial development defects.
心室心肌发育是一个精心编排的过程,涉及不同的心脏结构、多个信号通路和无数蛋白质。这一重要发育事件的失调会导致心肌病,如左心室心肌致密化不全,影响儿童和成人。人类和小鼠研究揭示了一些心肌病病例的病因,并突出了遗传和环境因素的作用。然而,心室心肌发育的调控仍未完全明确。锌是一种必需的微量金属,具有结构、酶促和信号功能。锌稳态的扰动会导致包括心肌病在内的发育和生理缺陷。在本综述中,我们总结了锌和锌转运体影响心室心肌发育调控的几种机制。基于我们的综述,我们提出锌缺乏和锌转运体突变可能是一些心肌病病例的基础,尤其是那些涉及心室心肌发育缺陷的病例。