Epigenetic Regulation of Endothelial Dysfunction and Inflammation in Pulmonary Arterial Hypertension.

Epigenetic Regulation of Endothelial Dysfunction and Inflammation in Pulmonary Arterial Hypertension.
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DOI:
10.3390/ijms222212098
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发表时间:
2021-11-09
影响因子:
5.6
通讯作者:
Farkas L
Farkas L
中科院分区:
生物学2区
文献类型:
--
作者:
Hudson J;Farkas L

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肺动脉高压(PAH)曾被认为是一种通过血管扩张治疗的疾病,但现在已成为一种伴有严重内皮细胞功能障碍的肺血管疾病。在缺乏治愈方法的情况下,许多研究试图了解EC调节的详细机制,以潜在地为PAH创造更多的治疗选择。内皮功能障碍的特征在于复杂的表型变化,包括不受抑制的增殖、增殖抵抗、增强的炎症信号传导和代谢重编程。最近的研究强调了表观遗传修饰的作用,导致促炎反应途径,内皮功能障碍和PAH的进展。本文综述了表观遗传机制,如DNA甲基化,组蛋白修饰,非编码RNA,这可能会导致异常的内皮功能的现有文献。我们的目标是为PAH背景下内皮细胞的免疫失调和表观遗传变化建立一个概念框架。这些研究以及其他研究可能会导致治疗这种毁灭性疾病的治疗方法的进步。
Once perceived as a disorder treated by vasodilation, pulmonary artery hypertension (PAH) has emerged as a pulmonary vascular disease with severe endothelial cell dysfunction. In the absence of a cure, many studies seek to understand the detailed mechanisms of EC regulation to potentially create more therapeutic options for PAH. Endothelial dysfunction is characterized by complex phenotypic changes including unchecked proliferation, apoptosis-resistance, enhanced inflammatory signaling and metabolic reprogramming. Recent studies have highlighted the role of epigenetic modifications leading to pro-inflammatory response pathways, endothelial dysfunction, and the progression of PAH. This review summarizes the existing literature on epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs, which can lead to aberrant endothelial function. Our goal is to develop a conceptual framework for immune dysregulation and epigenetic changes in endothelial cells in the context of PAH. These studies as well as others may lead to advances in therapeutics to treat this devastating disease.
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