Dittrich Anna M, Mienert Julia, Pott Julian, Engels Lena, Sinning Christoph, Hennigs Jan K, Klose Hans, Harbaum Lars
Division of Respiratory Medicine and Centre of Pulmonary Arterial Hypertension Hamburg, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Department of Cardiology, University Heart & Vascular Centre Hamburg, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
ERJ Open Res. 2023 Mar 13;9(2). doi: 10.1183/23120541.00528-2022. eCollection 2023 Mar.
Converging evidence from proteogenomic analyses prioritises thrombospondin-2 (TSP2) as a potential biomarker for idiopathic or heritable pulmonary arterial hypertension (PAH). We aimed to assess TSP2 levels in different forms of pulmonary hypertension (PH) and to define its clinical phenotype.
Absolute concentrations of TSP2 were quantified in plasma samples from a prospective single-centre cohort study including 196 patients with different forms of PH and 16 disease controls (suspected PH, but normal resting pulmonary haemodynamics). In an unbiased approach, TSP2 levels were related to 152 clinical variables.
Concentrations of TSP2 were increased in patients with PH disease controls (p<0.001 for group comparison). The discriminatory ability of TSP2 levels to distinguish between patients and controls was superior to that of N-terminal pro-brain natriuretic peptide (p=0.0023 for comparison of areas under the curve). Elevation of TSP2 levels was consistently found in subcategories of PAH, in PH due to lung disease and due to left heart disease. Phenotypically, TSP2 levels were robustly related to echocardiographic markers that indicate the right ventricular (RV) response to chronically increased afterload with increased levels in patients with impaired systolic function and ventriculoarterial uncoupling. Focusing on PAH, increased TSP2 levels were able to distinguish between adaptive and maladaptive RV phenotypes (area under the curve 0.87, 95% CI 0.76-0.98).
The study indicates that plasma TSP2 levels inform on the presence of PH and associate with clinically relevant RV phenotypes in the setting of increased afterload, which may provide insight into processes of RV adaptability.
蛋白质基因组分析的越来越多的证据将血小板反应蛋白-2（TSP2）列为特发性或遗传性肺动脉高压（PAH）的潜在生物标志物。我们旨在评估不同形式的肺动脉高压（PH）中TSP2的水平，并确定其临床表型。
在前瞻性单中心队列研究的血浆样本中对TSP2的绝对浓度进行定量，该研究包括196例不同形式的PH患者和16例疾病对照（疑似PH，但静息肺血流动力学正常）。采用无偏倚方法，将TSP2水平与152个临床变量相关联。
PH患者的TSP2浓度高于疾病对照（组间比较p<0.001）。TSP2水平区分患者和对照的鉴别能力优于N末端脑钠肽前体（曲线下面积比较p=0.0023）。在PAH的亚类、肺部疾病所致PH和左心疾病所致PH中均持续发现TSP2水平升高。在表型上，TSP2水平与超声心动图标志物密切相关，这些标志物表明右心室（RV）对慢性后负荷增加的反应，收缩功能受损和心室动脉解偶联患者的水平升高。聚焦于PAH，TSP2水平升高能够区分适应性和适应不良的RV表型（曲线下面积0.87，95%CI 0.76-0.98）。
该研究表明，血浆TSP2水平可反映PH的存在，并与后负荷增加情况下临床上相关的RV表型相关，这可能有助于深入了解RV适应性过程。
