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首页> 外文期刊>Pulmonary Circulation >Serum Osteoprotegerin is Increased and Predicts Survival in Idiopathic Pulmonary Arterial Hypertension:
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Serum Osteoprotegerin is Increased and Predicts Survival in Idiopathic Pulmonary Arterial Hypertension:

机译：血清骨保护素增加并预测特发性肺动脉高压的生存：

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We previously reported that osteoprotegerin (OPG) is regulated by pathways associated with pulmonary arterial hypertension (PAH), and is present at elevated levels within pulmonary vascular lesions and sera from patients with idiopathic PAH (IPAH). Since OPG is a naturally secreted protein, we investigated the relationship between serum OPG and disease severity and outcome in patients with IPAH and animal models. OPG mRNA expression was measured in pulmonary artery smooth muscle cells (PASMC) from pulmonary arteries of patients with and without IPAH. Serum concentrations of OPG were measured in a retrospective and prospective group of patients. OPG levels were compared with phenotypic data and other putative PAH biomarkers. Prognostic significance was assessed and levels compared with healthy controls. Correlation of OPG and pulmonary vascular remodeling was also performed in rodent models of PAH. OPG mRNA was significantly increased 2-fold in PASMC isolated from explanted PAH lungs compared with control. Serum OPG concentrations were markedly elevated in IPAH compared with controls. In Cohort 1 OPG levels significantly correlated with mean right atrial pressure and cardiac index, while in Cohort 2 significant correlations existed between age-adjusted OPG levels and gas transfer. In both cohorts an OPG concentration above a ROC-derived threshold of 4728 pg/ml predicted poorer survival. In two rodent models, OPG correlated with the degree of pulmonary vascular remodeling. OPG levels are significantly elevated in patients with idiopathic PAH and are of prognostic significance. The role of OPG as a potential biomarker and therapeutic target merits further investigation.
机译：我们以前曾报道过，骨保护素（OPG）受与肺动脉高压（PAH）相关的途径调节，并以自发性PAH（IPAH）患者的肺血管病变和血清中升高的水平存在。由于OPG是一种天然分泌的蛋白质，因此我们调查了IPAH和动物模型患者的血清OPG与疾病严重程度和预后之间的关系。在有和没有IPAH的患者的肺动脉中，在肺动脉平滑肌细胞（PASMC）中测量OPG mRNA的表达。在回顾性和前瞻性患者组中测量OPG的血清浓度。将OPG水平与表​​型数据和其他假定的PAH生物标志物进行比较。评估预后的意义，并与健康对照组进行比较。在PAH的啮齿动物模型中还进行了OPG与肺血管重塑的相关性。与对照组相比，从移植的PAH肺中分离出的PASMC中OPG mRNA显着增加了2倍。与对照组相比，IPAH中的血清OPG浓度显着升高。在队列1中，OPG水平与平均右心房压力和心脏指数显着相关，而在队列2中，年龄校正的OPG水平与气体转移之间存在显着相关性。在这两个队列中，高于ROC衍生阈值4728 pg / ml的OPG浓度都预示着较差的生存率。在两个啮齿动物模型中，OPG与肺血管重塑程度相关。特发性PAH患者的OPG水平显着升高，并具有预后意义。 OPG作为潜在生物标志物和治疗靶标的作用值得进一步研究。

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