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心血管疾病中的表观遗传调控:机制与临床试验进展。

Epigenetic regulation in cardiovascular disease: mechanisms and advances in clinical trials.

机构信息

The Eighth Affiliated Hospital, Sun Yat-sen University, No. 3025, Shennan Middle Rd, Futian District, 518033, Shenzhen, China.

Shenzhen Center for Disease Control and Prevention, 518055, Shenzhen, China.

出版信息

Signal Transduct Target Ther. 2022 Jun 25;7(1):200. doi: 10.1038/s41392-022-01055-2.

Abstract

Epigenetics is closely related to cardiovascular diseases. Genome-wide linkage and association analyses and candidate gene approaches illustrate the multigenic complexity of cardiovascular disease. Several epigenetic mechanisms, such as DNA methylation, histone modification, and noncoding RNA, which are of importance for cardiovascular disease development and regression. Targeting epigenetic key enzymes, especially the DNA methyltransferases, histone methyltransferases, histone acetylases, histone deacetylases and their regulated target genes, could represent an attractive new route for the diagnosis and treatment of cardiovascular diseases. Herein, we summarize the knowledge on epigenetic history and essential regulatory mechanisms in cardiovascular diseases. Furthermore, we discuss the preclinical studies and drugs that are targeted these epigenetic key enzymes for cardiovascular diseases therapy. Finally, we conclude the clinical trials that are going to target some of these processes.

摘要

表观遗传学与心血管疾病密切相关。全基因组连锁和关联分析以及候选基因方法说明了心血管疾病的多基因复杂性。几种表观遗传机制,如 DNA 甲基化、组蛋白修饰和非编码 RNA,对心血管疾病的发生和消退都很重要。针对表观遗传关键酶,特别是 DNA 甲基转移酶、组蛋白甲基转移酶、组蛋白乙酰转移酶、组蛋白去乙酰化酶及其调控的靶基因,可能代表了心血管疾病诊断和治疗的一个有吸引力的新途径。本文总结了心血管疾病中表观遗传学历史和基本调控机制的知识。此外,我们还讨论了针对这些表观遗传关键酶治疗心血管疾病的临床前研究和药物。最后,我们总结了一些针对这些过程的临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be56/9233709/92430f02b732/41392_2022_1055_Fig1_HTML.jpg

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