Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029, USA.
Cells. 2021 Mar 13;10(3):638. doi: 10.3390/cells10030638.
Pulmonary arterial hypertension (PAH) is a rare and chronic lung disease characterized by progressive occlusion of the small pulmonary arteries, which is associated with structural and functional alteration of the smooth muscle cells and endothelial cells within the pulmonary vasculature. Excessive vascular remodeling is, in part, responsible for high pulmonary vascular resistance and the mean pulmonary arterial pressure, increasing the transpulmonary gradient and the right ventricular "pressure overload", which may result in right ventricular (RV) dysfunction and failure. Current technological advances in multi-omics approaches, high-throughput sequencing, and computational methods have provided valuable tools in molecular profiling and led to the identification of numerous genetic variants in PAH patients. In this review, we summarized the pathogenesis, classification, and current treatments of the PAH disease. Additionally, we outlined the latest next-generation sequencing technologies and the consequences of common genetic variants underlying PAH susceptibility and disease progression. Finally, we discuss the importance of molecular genetic testing for precision medicine in PAH and the future of genomic medicines, including gene-editing technologies and gene therapies, as emerging alternative approaches to overcome genetic disorders in PAH.
肺动脉高压（PAH）是一种罕见的慢性肺部疾病，其特征为小肺动脉进行性闭塞，这与肺血管中的平滑肌细胞和内皮细胞的结构和功能改变有关。血管过度重塑是导致肺血管阻力和平均肺动脉压升高的部分原因，从而增加了肺循环梯度和右心室“压力超负荷”，这可能导致右心室（RV）功能障碍和衰竭。多组学方法、高通量测序和计算方法等当前技术进步为分子分析提供了有价值的工具，并导致在 PAH 患者中鉴定出许多遗传变异。在这篇综述中，我们总结了 PAH 疾病的发病机制、分类和当前治疗方法。此外，我们概述了最新的下一代测序技术以及导致 PAH 易感性和疾病进展的常见遗传变异的后果。最后，我们讨论了分子遗传学检测在 PAH 精准医学中的重要性，以及基因组医学的未来，包括基因编辑技术和基因治疗，作为克服 PAH 遗传障碍的新兴替代方法。
