Notch 信号通路在胸主动脉瘤发病机制中的作用：胚胎与成体状态间的桥梁。

Notch signaling in the pathogenesis of thoracic aortic aneurysms: A bridge between embryonic and adult states.

机构信息

Almazov National Medical Research Centre, Akkuratova, 2, 197341 Saint Petersburg, Russia; Institute of Cytology, Russian Academy of Sciences, Tikhoretskiy, 4, 194064 Saint Petersburg, Russia; Saint Petersburg State University, Department of Embryology, Universitetskaya nab., 7/9, 199034, Saint Petersburg, Russia.

Almazov National Medical Research Centre, Akkuratova, 2, 197341 Saint Petersburg, Russia; Institute of Cytology, Russian Academy of Sciences, Tikhoretskiy, 4, 194064 Saint Petersburg, Russia.

出版信息

Biochim Biophys Acta Mol Basis Dis. 2020 Mar 1;1866(3):165631. doi: 10.1016/j.bbadis.2019.165631. Epub 2019 Dec 6.

DOI:10.1016/j.bbadis.2019.165631

PMID:31816439

Abstract

Aneurysms of the thoracic aorta are a "silent killer" with no evident clinical signs until the fatal outcome. Molecular and genetic bases of thoracic aortic aneurysms mainly include transforming growth factor beta signaling, smooth muscle contractile units and metabolism genes, and extracellular matrix genes. In recent studies, a role of Notch signaling, among other pathways, has emerged in disease pathogenesis. Notch is a highly conserved signaling pathway that regulates the development and differentiation of many types of tissues and influences major cellular processes such as cell proliferation, differentiation and apoptosis. Mutations in several Notch signaling components have been associated with a number of heart defects, demonstrating an essential role of Notch signaling both in cardiovascular system development and its maintenance during postnatal life. This review discusses the role of Notch signaling in the pathogenesis of thoracic aortic aneurysms considering development and maintenance of the aortic root and how developmental regulations by Notch signaling may influence thoracic aortic aneurysms.

摘要

胸主动脉瘤是一种“沉默的杀手”，在致命后果出现之前没有明显的临床迹象。胸主动脉瘤的分子和遗传基础主要包括转化生长因子-β信号、平滑肌收缩单位和代谢基因以及细胞外基质基因。在最近的研究中，Notch 信号通路等途径在疾病发病机制中的作用已经显现出来。Notch 是一种高度保守的信号通路，它调节多种组织的发育和分化，并影响细胞增殖、分化和凋亡等主要细胞过程。几种 Notch 信号成分的突变与多种心脏缺陷有关，这表明 Notch 信号在心血管系统发育及其在出生后生命过程中的维持中都具有重要作用。本文讨论了 Notch 信号在胸主动脉瘤发病机制中的作用，考虑了主动脉根部的发育和维持，以及 Notch 信号的发育调控如何影响胸主动脉瘤。