Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA ; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA ; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA ; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Pulm Circ. 2014 Jun;4(2):269-79. doi: 10.1086/675990.
The pathophysiologic alterations of patients with pulmonary arterial hypertension (PAH) are diverse. We aimed to determine novel pathogenic pathways from circulating proteins in patients with PAH. Multianalyte profiling (MAP) was used to measure 90 specifically selected antigens in the plasma of 113 PAH patients and 51 control patients. Erythropoietin (EPO) functional activity was assessed via in vitro pulmonary artery endothelial cell networking and smooth muscle cell proliferation assays. Fifty-eight patients had idiopathic PAH, whereas 55 had other forms of PAH; 5 had heritable PAH, 18 had connective tissue disease (15 with scleroderma and 3 with lupus erythematosis), 13 had portopulmonary hypertension, 6 had PAH associated with drugs or toxins, and 5 had congenital heart disease. The plasma-antigen profile of PAH revealed increased levels of several novel biomarkers, including EPO. Immune quantitative and histochemical studies revealed that EPO not only was significantly elevated in the plasma of PAH patients but also promoted pulmonary artery endothelial cell network formation and smooth muscle cell proliferation. MAP is a hypothesis-generating approach to identifying novel pathophysiologic pathways in PAH. EPO is upregulated in the circulation and lungs of patients with PAH and may affect endothelial and smooth muscle cell proliferation.
肺动脉高压（PAH）患者的病理生理改变多种多样。我们旨在从 PAH 患者的循环蛋白中确定新的致病途径。采用多分析物分析（MAP）测量 113 例 PAH 患者和 51 例对照患者血浆中 90 种特定选择的抗原。通过体外肺动脉内皮细胞网络和平滑肌细胞增殖测定评估促红细胞生成素（EPO）的功能活性。58 例患者为特发性 PAH，55 例为其他类型的 PAH；5 例为遗传性 PAH，18 例为结缔组织病（15 例为硬皮病，3 例为红斑狼疮），13 例为门脉高压性 PAH，6 例为与药物或毒素相关的 PAH，5 例为先天性心脏病。PAH 的血浆抗原谱显示出几种新型生物标志物的水平升高，包括 EPO。免疫定量和组织化学研究表明，EPO 不仅在 PAH 患者的血浆中显著升高，而且还促进肺血管内皮细胞网络形成和平滑肌细胞增殖。MAP 是一种假设生成方法，用于识别 PAH 中的新病理生理途径。EPO 在 PAH 患者的循环和肺部中上调，可能影响内皮细胞和平滑肌细胞的增殖。
