Department of Cell Biology and Anatomy, New York Medical College, 15 Dana Road, BSB 131A, Valhalla, NY, 10595, USA.
Department of Physiology, New York Medical College, 15 Dana Road, BSB 131A, Valhalla, NY, 10595, USA.
J Transl Med. 2023 Jul 17;21(1):477. doi: 10.1186/s12967-023-04339-5.
Pulmonary arterial hypertension (PAH) is a multifactorial disease associated with the remodeling of pulmonary blood vessels. If left unaddressed, PAH can lead to right heart failure and even death. Multiple biological processes, such as smooth muscle proliferation, endothelial dysfunction, inflammation, and resistance to apoptosis, are associated with PAH. Increasing evidence suggests that epigenetic factors play an important role in PAH by regulating the chromatin structure and altering the expression of critical genes. For example, aberrant DNA methylation and histone modifications such as histone acetylation and methylation have been observed in patients with PAH and are linked to vascular remodeling and pulmonary vascular dysfunction. In this review article, we provide a comprehensive overview of the role of key epigenetic targets in PAH pathogenesis, including DNA methyltransferase (DNMT), ten-eleven translocation enzymes (TET), switch-independent 3A (SIN3A), enhancer of zeste homolog 2 (EZH2), histone deacetylase (HDAC), and bromodomain-containing protein 4 (BRD4). Finally, we discuss the potential of multi-omics integration to better understand the molecular signature and profile of PAH patients and how this approach can help identify personalized treatment approaches.
肺动脉高压（PAH）是一种与肺血管重构相关的多因素疾病。如果不加以治疗，PAH 可导致右心衰竭甚至死亡。多种生物学过程，如平滑肌增殖、内皮功能障碍、炎症和抗凋亡，与 PAH 相关。越来越多的证据表明，表观遗传因素通过调节染色质结构和改变关键基因的表达，在 PAH 中发挥重要作用。例如，在 PAH 患者中观察到异常的 DNA 甲基化和组蛋白修饰，如组蛋白乙酰化和甲基化，与血管重构和肺血管功能障碍有关。在这篇综述文章中，我们全面概述了关键表观遗传靶点在 PAH 发病机制中的作用，包括 DNA 甲基转移酶（DNMT）、十-十一易位酶（TET）、无开关 3A（SIN3A）、增强子结合锌指蛋白 2（EZH2）、组蛋白脱乙酰酶（HDAC）和溴结构域蛋白 4（BRD4）。最后，我们讨论了多组学整合的潜力，以更好地了解 PAH 患者的分子特征和特征，并探讨这种方法如何帮助确定个性化的治疗方法。
