Department of Molecular Genetics, Faculty of Sciences and Engineering, Maastricht University, 6229 ER Maastricht, The Netherlands.
CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands.
Int J Mol Sci. 2020 Nov 24;21(23):8901. doi: 10.3390/ijms21238901.
Pulmonary artery hypertension (PAH) is a rare chronic disease with high impact on patients' quality of life and currently no available cure. PAH is characterized by constant remodeling of the pulmonary artery by increased proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), fibroblasts (FBs) and endothelial cells (ECs). This remodeling eventually leads to increased pressure in the right ventricle (RV) and subsequent right ventricle hypertrophy (RVH) which, when left untreated, progresses into right ventricle failure (RVF). PAH can not only originate from heritable mutations, but also develop as a consequence of congenital heart disease, exposure to drugs or toxins, HIV, connective tissue disease or be idiopathic. While much attention was drawn into investigating and developing therapies related to the most well understood signaling pathways in PAH, in the last decade, a shift towards understanding the epigenetic mechanisms driving the disease occurred. In this review, we reflect on the different epigenetic regulatory factors that are associated with the pathology of RV remodeling, and on their relevance towards a better understanding of the disease and subsequently, the development of new and more efficient therapeutic strategies.
肺动脉高压（PAH）是一种罕见的慢性疾病，对患者的生活质量有很大影响，目前尚无治愈方法。PAH 的特征是肺动脉不断重塑，肺动脉平滑肌细胞（PASMCs）、成纤维细胞（FBs）和内皮细胞（ECs）增殖和迁移增加。这种重塑最终导致右心室（RV）压力升高，随后出现右心室肥厚（RVH），如果不加治疗，会进展为右心衰竭（RVF）。PAH 不仅可以源自遗传性突变，也可以作为先天性心脏病、暴露于药物或毒素、HIV、结缔组织疾病的结果而发生，或者是特发性的。虽然人们对与 PAH 中最易理解的信号通路相关的治疗方法进行了大量研究，但在过去十年中，人们的注意力转向了理解导致疾病的表观遗传机制。在这篇综述中，我们反思了与 RV 重塑病理学相关的不同表观遗传调节因子，以及它们对更好地理解疾病的相关性，以及随后开发新的、更有效的治疗策略的相关性。
