Harbaum Lars, Rhodes Christopher J, Otero-Núñez Pablo, Wharton John, Wilkins Martin R
National Heart and Lung Institute, Imperial College London, London, UK.
Br J Pharmacol. 2021 Jan;178(1):108-120. doi: 10.1111/bph.15056. Epub 2020 Apr 28.
Recent genome-wide analyses of rare and common sequence variations have brought greater clarity to the genetic architecture of pulmonary arterial hypertension and implicated novel genes in disease development. Transcriptional signatures have been reported in whole lung tissue, pulmonary vascular cells and peripheral circulating cells. High-throughput platforms for plasma proteomics and metabolomics have identified novel biomarkers associated with clinical outcomes and provided molecular instruments for risk assessment. There are methodological challenges to integrating these datasets, coupled to statistical power limitations inherent to the study of a rare disease, but the expectation is that this approach will reveal novel druggable targets and biomarkers that will open the way to personalized medicine. Here, we review the current state-of-the-art and future promise of 'omics' in the field of translational medicine in pulmonary arterial hypertension. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc.
近期针对罕见和常见序列变异的全基因组分析,使肺动脉高压的遗传结构更加清晰,并发现了与疾病发展相关的新基因。在全肺组织、肺血管细胞和外周循环细胞中均已报道了转录特征。血浆蛋白质组学和代谢组学的高通量平台已鉴定出与临床结局相关的新型生物标志物,并为风险评估提供了分子工具。整合这些数据集存在方法学挑战,同时罕见病研究固有的统计效力限制也存在,但人们期望这种方法将揭示新的可成药靶点和生物标志物,从而为个性化医疗开辟道路。在此,我们综述了肺动脉高压转化医学领域中“组学”的当前技术水平和未来前景。相关文章:本文是关于心脏保护中的危险因素、合并症和辅助用药的主题问题的一部分。要查看本节中的其他文章,请访问http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc。