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将表观遗传机制作为肺动脉高压疾病的一种新兴治疗策略。

Targeting epigenetic mechanisms as an emerging therapeutic strategy in pulmonary hypertension disease.

作者信息

Bisserier Malik, Janostiak Radoslav, Lezoualc'h Frank, Hadri Lahouaria

机构信息

Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.

出版信息

Vasc Biol. 2020 Jan;2(1):R17-R34. doi: 10.1530/vb-19-0030. Epub 2020 Jan 9.

Abstract

Pulmonary arterial hypertension (PAH) is a multifactorial cardiopulmonary disease characterized by an elevation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR), which can lead to right ventricular (RV) failure, multi-organ dysfunction, and ultimately to premature death. Despite the advances in molecular biology, the mechanisms underlying pulmonary hypertension (PH) remain unclear. Nowadays, there is no curative treatment for treating PH. Therefore, it is crucial to identify novel, specific therapeutic targets and to offer more effective treatments against the progression of PH. Increasing amounts of evidence suggest that epigenetic modification may play a critical role in the pathogenesis of PAH. In the presented paper, we provide an overview of the epigenetic mechanisms specifically, DNA methylation, histone acetylation, histone methylation, and ncRNAs. As the recent identification of new pharmacological drugs targeting these epigenetic mechanisms has opened new therapeutic avenues, we also discuss the importance of epigenetic-based therapies in the context of PH.

摘要

肺动脉高压(PAH)是一种多因素的心肺疾病,其特征是肺动脉压力(PAP)和肺血管阻力(PVR)升高,可导致右心室(RV)衰竭、多器官功能障碍,并最终导致过早死亡。尽管分子生物学取得了进展,但肺动脉高压(PH)的潜在机制仍不清楚。目前,尚无治疗PH的治愈性疗法。因此,确定新的、特异性治疗靶点并提供更有效的治疗以对抗PH的进展至关重要。越来越多的证据表明,表观遗传修饰可能在PAH的发病机制中起关键作用。在本文中,我们具体概述了表观遗传机制,即DNA甲基化、组蛋白乙酰化、组蛋白甲基化和非编码RNA。由于最近针对这些表观遗传机制的新型药理学药物的鉴定开辟了新的治疗途径,我们还讨论了基于表观遗传的疗法在PH背景下的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d92/7439929/80859b632d53/VB-19-0030fig1.jpg

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