The role of histone modifications in pulmonary hypertension: From mechanisms to therapeutic targets

IF 3.5 3区医学 Q2 PHARMACOLOGY & PHARMACY

Vascular pharmacology Pub Date : 2025-06-25 DOI:10.1016/j.vph.2025.107519

Yunhua Yang , Shaoxin Gong , Na Liang , Zhouxin Li , Xiaoyu Duan , Tong Xie , Xiaoyong Lei , Aiping Wang

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Abstract

Pulmonary hypertension is a progressive vascular disease characterized by pulmonary vascular remodeling, with high mortality and poor prognosis despite advances in medical therapy. Recently, histone modification therapies for pulmonary hypertension have received more attention. Studies have shown that abnormal histone modifications and the enzymes responsible for these alterations can drive pulmonary vascular cell proliferation, migration, and anti-apoptosis by regulating chromatin structure and gene expression, thereby promoting pulmonary vascular remodeling in pulmonary hypertension. This review illustrates histone modifications, including methylation, acetylation, lactylation, and SUMOylation, and the enzymes responsible for these modifications, exploring their role and pathophysiological mechanism in pulmonary hypertension. In addition, the review summarizes the small molecule modulators currently under development and their efficacy in various preclinical models of pulmonary hypertension. Comprehending the function of histone modifications in pulmonary hypertension will help identify new biomarkers and molecular targets and facilitate personalized treatments for this severe disease.

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组蛋白修饰在肺动脉高压中的作用：从机制到治疗靶点。

肺动脉高压是一种以肺血管重构为特征的进行性血管疾病，尽管药物治疗取得了进展，但其死亡率高，预后差。近年来，组蛋白修饰治疗肺动脉高压受到越来越多的关注。研究表明，组蛋白异常修饰及其相关酶可通过调控染色质结构和基因表达，驱动肺血管细胞增殖、迁移和抗凋亡，从而促进肺动脉高压患者肺血管重构。本文综述了组蛋白修饰，包括甲基化、乙酰化、乳酸化和SUMOylation，以及负责这些修饰的酶，探讨了它们在肺动脉高压中的作用和病理生理机制。此外，综述了目前正在开发的小分子调节剂及其在各种肺动脉高压临床前模型中的疗效。了解组蛋白修饰在肺动脉高压中的功能将有助于确定新的生物标志物和分子靶点，并促进对这种严重疾病的个性化治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Vascular pharmacology 医学-药学

CiteScore

6.60

自引率

2.50%

发文量

153

审稿时长

31 days

期刊介绍： Vascular Pharmacology publishes papers, which contains results of all aspects of biology and pharmacology of the vascular system. Papers are encouraged in basic, translational and clinical aspects of Vascular Biology and Pharmacology, utilizing approaches ranging from molecular biology to integrative physiology. All papers are in English. The Journal publishes review articles which include vascular aspects of thrombosis, inflammation, cell signalling, atherosclerosis, and lipid metabolism.