Targeted proteomics of right heart adaptation to pulmonary arterial hypertension.
Targeted proteomics of right heart adaptation to pulmonary arterial hypertension.
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DOI：
10.1183/13993003.02428-2020
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发表时间：
2021-04
期刊：
影响因子：
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通讯作者：
Zamanian RT
中科院分区：
文献类型：
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作者：
Amsallem M;Sweatt AJ;Arthur Ataam J;Guihaire J;Lecerf F;Lambert M;Ghigna MR;Ali MK;Mao Y;Fadel E;Rabinovitch M;de Jesus Perez V;Spiekerkoetter E;Mercier O;Haddad F;Zamanian RT
以前没有蛋白质组学筛选研究集中在肺动脉高压（PAH）的右心室（RV）。本研究探讨了PAH患者右心适应不良表型（RHMP）相关的循环蛋白质组学特征。在121例（发现队列）和76例（验证队列）PAH患者中使用多重免疫测定法进行血浆蛋白质组学分析。通过偏最小二乘回归评估蛋白质组学标志物与RHMP之间的相关性，由马约右心评分（结合RV应变、纽约心脏协会（NYHA）分级和N末端脑钠肽前体（NT-proBNP））和斯坦福大学评分（RV收缩末期重构指数、NYHA分级和NT-proBNP）定义。在PAH患者和对照组以及肺动脉束带（PAB）小鼠的RV样本中测量生物标志物表达。在两个队列中，高水平的肝细胞生长因子（HGF）、干细胞生长因子-β、神经生长因子和基质衍生因子-1与马约和斯坦福大学评分较差相关，与肺阻力或压力无关（验证队列具有更严重的疾病特征：心脏指数较低和NT-proBNP较高）。在两个队列中，HGF增加了REVEAL评分在3年时死亡、移植或住院的预测价值。 终末期PAH患者的RV HGF及其受体c-Met表达水平高于对照组，PAB小鼠的RV HGF及其受体c-Met表达水平高于假手术组。高血浆HGF水平与RHMP相关，可预测3年临床恶化。PAH患者的HGF和c-Met RV表达水平均升高。评估血浆肝细胞生长因子水平可能会发现有心力衰竭风险的患者，这些患者需要更密切的随访和强化治疗。高血浆HGF水平与PAH右心适应不良表型和预后相关。HGF和c-Met RV表达均增加。评估血浆肝细胞生长因子水平可能会发现患者谁值得密切随访和强化治疗。https://bit.ly/3djiy9O
No prior proteomic screening study has centred on the right ventricle (RV) in pulmonary arterial hypertension (PAH). This study investigates the circulating proteomic profile associated with right heart maladaptive phenotype (RHMP) in PAH. Plasma proteomic profiling was performed using multiplex immunoassay in 121 (discovery cohort) and 76 (validation cohort) PAH patients. The association between proteomic markers and RHMP, defined by the Mayo right heart score (combining RV strain, New York Heart Association (NYHA) class and N-terminal pro-brain natriuretic peptide (NT-proBNP)) and Stanford score (RV end-systolic remodelling index, NYHA class and NT-proBNP), was assessed by partial least squares regression. Biomarker expression was measured in RV samples from PAH patients and controls, and pulmonary artery banding (PAB) mice. High levels of hepatocyte growth factor (HGF), stem cell growth factor-β, nerve growth factor and stromal derived factor-1 were associated with worse Mayo and Stanford scores independently from pulmonary resistance or pressure in both cohorts (the validation cohort had more severe disease features: lower cardiac index and higher NT-proBNP). In both cohorts, HGF added value to the REVEAL score in the prediction of death, transplant or hospitalisation at 3 years. RV expression levels of HGF and its receptor c-Met were higher in end-stage PAH patients than controls, and in PAB mice than shams. High plasma HGF levels are associated with RHMP and predictive of 3-year clinical worsening. Both HGF and c-Met RV expression levels are increased in PAH. Assessing plasma HGF levels might identify patients at risk of heart failure who warrant closer follow-up and intensified therapy. High plasma HGF levels are associated with right heart maladaptive phenotype and prognosis in PAH. HGF and c-Met RV expression are both increased. Assessing plasma HGF levels might identify patients who warrant closer follow-up and intensified therapy. https://bit.ly/3djiy9O