Department of Cardiology, 2141 Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
CAG Center for Endotheliomics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Sci Rep. 2022 Aug 2;12(1):13284. doi: 10.1038/s41598-022-17374-x.
Pulmonary hypertension (PH) is classified into five clinical diagnostic groups, including group 1 [idiopathic pulmonary arterial hypertension (IPAH) and connective tissue disease-associated PAH (CTD-aPAH)] and group 4 (chronic thromboembolic pulmonary hypertension (CTEPH)). PH is a progressive, life-threatening, incurable disease. The pathological mechanisms underlying PH remain elusive; recent evidence has revealed that abnormal metabolic activities in the endothelium may play a crucial role. This research introduces a novel approach for studying PH endothelial function, building on the genome-scale metabolic reconstruction of the endothelial cell (EC) to investigate intracellular metabolism. We demonstrate that the intracellular metabolic activities of ECs in PH patients cluster into four phenotypes independent of the PH diagnosis. Notably, the disease severity differs significantly between the metabolic phenotypes, suggesting their clinical relevance. The significant metabolic differences between the PH phenotypes indicate that they may require different therapeutic interventions. In addition, diagnostic capabilities enabling their identification is warranted to investigate whether this opens a novel avenue of precision medicine.
肺动脉高压（PH）分为五个临床诊断组，包括第 1 组[特发性肺动脉高压（IPAH）和结缔组织病相关肺动脉高压（CTD-aPAH）]和第 4 组（慢性血栓栓塞性肺动脉高压（CTEPH））。PH 是一种进行性的、危及生命的、无法治愈的疾病。PH 的病理机制仍不清楚；最近的证据表明，内皮细胞异常的代谢活动可能起着关键作用。本研究在对内皮细胞（EC）进行基因组规模代谢重建以研究细胞内代谢的基础上，介绍了一种研究 PH 内皮功能的新方法。我们证明，PH 患者的 EC 细胞内代谢活动可分为四个表型，与 PH 诊断无关。值得注意的是，代谢表型之间的疾病严重程度有显著差异，提示其具有临床相关性。PH 表型之间的显著代谢差异表明，它们可能需要不同的治疗干预。此外，需要有诊断能力来识别这些表型，以研究这是否为精准医学开辟了新途径。
