Wellbrock Jasmin, Harbaum Lars, Stamm Hauke, Hennigs Jan K, Schulz Björn, Klose Hans, Bokemeyer Carsten, Fiedler Walter, Lüneburg Nicole
Department of Hematology, Oncology and Stem Cell Transplantation with Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany,
Lung. 2015 Aug;193(4):567-70. doi: 10.1007/s00408-015-9735-5. Epub 2015 Apr 30.
Gremlin-1, an intrinsic antagonist of bone morphogenetic protein (BMP) signaling, has been implicated in the pathophysiology of pulmonary arterial hypertension (PAH). However, it is unknown whether gremlin-1 can be detected in the circulation of PAH patients and whether it is associated with patients' functional status and outcome. With a mean level of 242 ± 24 ng/ml, gremlin-1 levels of 31 PAH patients were significantly elevated compared to 151 ± 18 ng/ml in 15 age- and gender-matched healthy subject (p = 0.016). In PAH patients, increasing gremlin-1 levels correlated with N-terminal prohormone of brain natriuretic peptide levels (r = 0.608, p < 0.001) and inversely with the 6-minute walking distance (r = -0.412, p = 0.029). Furthermore, gremlin-1 significantly stratified survival in PAH patients (p = 0.015). Gremlin-1 may represent a new biomarker for PAH which can be linked directly to the underlying pathomechanism. Elevated levels of gremlin-1 are associated with patients' functional status and survival, thus gremlin-1 neutralization could represent a potential therapeutic strategy to increase BMPR2 signaling.
Gremlin-1是骨形态发生蛋白（BMP）信号通路的一种内源性拮抗剂，已被证实与肺动脉高压（PAH）的病理生理学有关。然而，目前尚不清楚PAH患者的循环系统中是否能检测到Gremlin-1，以及它是否与患者的功能状态和预后相关。31例PAH患者的Gremlin-1水平平均为242±24 ng/ml，显著高于15例年龄和性别匹配的健康受试者（151±18 ng/ml，p = 0.016）。在PAH患者中，Gremlin-1水平的升高与脑钠肽前体N端水平相关（r = 0.608，p < 0.001），与6分钟步行距离呈负相关（r = -0.412，p = 0.029）。此外，Gremlin-1在PAH患者的生存分层中具有显著意义（p = 0.015）。Gremlin-1可能是PAH的一种新生物标志物，可直接与潜在的发病机制相关联。Gremlin-1水平升高与患者的功能状态和生存相关，因此中和Gremlin-1可能是一种增加BMPR2信号传导的潜在治疗策略。
