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转录因子在血管疾病发病机制及治疗靶点中的作用。

The role of transcription factors in the pathogenesis and therapeutic targeting of vascular diseases.

作者信息

Hu Poyi, Du Yifan, Xu Ying, Ye Ping, Xia Jiahong

机构信息

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Institute of Reproduction Health Research, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Cardiovasc Med. 2024 Apr 30;11:1384294. doi: 10.3389/fcvm.2024.1384294. eCollection 2024.

Abstract

Transcription factors (TFs) constitute an essential component of epigenetic regulation. They contribute to the progression of vascular diseases by regulating epigenetic gene expression in several vascular diseases. Recently, numerous regulatory mechanisms related to vascular pathology, ranging from general TFs that are continuously activated to histiocyte-specific TFs that are activated under specific circumstances, have been studied. TFs participate in the progression of vascular-related diseases by epigenetically regulating vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). The Krüppel-like family (KLF) TF family is widely recognized as the foremost regulator of vascular diseases. KLF11 prevents aneurysm progression by inhibiting the apoptosis of VSMCs and enhancing their contractile function. The presence of KLF4, another crucial member, suppresses the progression of atherosclerosis (AS) and pulmonary hypertension by attenuating the formation of VSMCs-derived foam cells, ameliorating endothelial dysfunction, and inducing vasodilatory effects. However, the mechanism underlying the regulation of the progression of vascular-related diseases by TFs has remained elusive. The present study categorized the TFs involved in vascular diseases and their regulatory mechanisms to shed light on the potential pathogenesis of vascular diseases, and provide novel insights into their diagnosis and treatment.

摘要

转录因子(TFs)是表观遗传调控的重要组成部分。它们通过调节多种血管疾病中的表观遗传基因表达,促进血管疾病的发展。近来,人们对众多与血管病理相关的调控机制进行了研究,这些机制涵盖了从持续激活的一般转录因子到特定情况下被激活的组织细胞特异性转录因子。转录因子通过对血管内皮细胞(VECs)和平滑肌细胞(VSMCs)进行表观遗传调控,参与血管相关疾病的发展进程。Krüppel样家族(KLF)转录因子家族被广泛认为是血管疾病的首要调节因子。KLF11通过抑制血管平滑肌细胞凋亡并增强其收缩功能,阻止动脉瘤的发展。另一个关键成员KLF4的存在,通过减少血管平滑肌细胞衍生的泡沫细胞形成、改善内皮功能障碍和诱导血管舒张作用,抑制动脉粥样硬化(AS)和肺动脉高压的发展。然而,转录因子调控血管相关疾病发展的机制仍不清楚。本研究对参与血管疾病的转录因子及其调控机制进行了分类,以阐明血管疾病的潜在发病机制,并为其诊断和治疗提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e9f/11091331/fa069ee78879/fcvm-11-1384294-g001.jpg

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