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GATA结合蛋白5在心血管疾病中的潜在作用。

Potential roles of GATA binding protein 5 in cardiovascular diseases.

作者信息

Song Zhi-Peng, Yan Bo

机构信息

Department of Medicine, Shandong University School of Medicine, Jinan, Shandong, 250014, P. R. China.

The Center for Molecular Genetics of Cardiovascular Diseases, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272000, P. R. China.

出版信息

Rev Cardiovasc Med. 2020 Jun 30;21(2):253-261. doi: 10.31083/j.rcm.2020.02.5104.

Abstract

It is known that functional defects of GATA binding protein 5 (GATA5), an important member of GATA transcription factor family, could cause multiple congenital defects. However, the mechanisms of this transcription factor in cardiovascular diseases are still little known. Finding a genetic approach should help with understanding the possible roles of GATA5 in different cardiovascular diseases and purpose it as a possible therapeutic agent. Hence, this review is divided into three chapters to summarize the roles and main regulatory mechanisms of GATA5 in hypertension, arrhythmia and congenital heart disease, respectively. In each chapter, this review firstly introduces the roles of mutations, and then discusses the main regulatory mechanisms of GATA5 in the corresponding diseases (Such as the endothelial dysfunction signaling pathway in the chapter of hypertension, GATA5-NaV1.5 signaling pathway in the chapter of arrhythmia, GATA5-HEY2 and GATA5-Nodal signaling pathway in the chapter of congenital heart disease). Additionally, based on these regulatory networks, it is also speculated that abnormal methylation of the gene promoter may lead to cardiovascular diseases such as congenital heart disease. This conjecture is proposed to enrich the regulatory networks of GATA5 and provide a theoretical basis for diagnosis and treatment of cardiovascular diseases.

摘要

已知GATA转录因子家族的重要成员GATA结合蛋白5(GATA5)的功能缺陷可导致多种先天性缺陷。然而,这种转录因子在心血管疾病中的机制仍鲜为人知。找到一种遗传学方法应有助于理解GATA5在不同心血管疾病中的可能作用,并将其作为一种可能的治疗药物。因此,本综述分为三章,分别总结GATA5在高血压、心律失常和先天性心脏病中的作用及主要调控机制。在每一章中,本综述首先介绍突变的作用,然后讨论GATA5在相应疾病中的主要调控机制(如高血压章节中的内皮功能障碍信号通路、心律失常章节中的GATA5-NaV1.5信号通路、先天性心脏病章节中的GATA5-HEY2和GATA5-Nodal信号通路)。此外,基于这些调控网络,还推测基因启动子的异常甲基化可能导致先天性心脏病等心血管疾病。提出这一推测是为了丰富GATA5的调控网络,并为心血管疾病的诊断和治疗提供理论依据。

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