Division of Respirology, Western University, London, ON, Canada.
Toronto Lung Transplant Program, University of Toronto, Toronto, ON, Canada.
Respirology. 2019 Nov;24(11):1104-1110. doi: 10.1111/resp.13557. Epub 2019 Apr 8.
Osteopontin (OPN) is a pleiotropic cytokine involved in the proliferation of pulmonary artery smooth muscle cells (PA-SMC). OPN is upregulated in the lungs of patients with pulmonary hypertension (PH) associated with pulmonary fibrosis, suggesting that the lung is a source of OPN. We hypothesized that OPN lung expression is elevated in Group I pulmonary arterial hypertension (PAH) and is correlated to haemodynamics.
Microarray analysis (Affymetrix) was performed after RNA was extracted from explanted lungs in 15 patients with Group I PAH who underwent lung transplantation (LTx) and 11 normal controls. PA pressure levels were recorded intraoperatively, immediately before starting LTx. Serum OPN levels were measured in subjects with PAH, Group II PH and normal controls on the day of right heart catheterization.
OPN was among the top five upregulated genes in PAH compared to normal controls, which was confirmed by reverse transcription polymerase chain reaction (RT-PCR). OPN expression was similar and equally elevated in different subtypes of PAH. A strong significant correlation was observed between mean pulmonary arterial pressure and OPN gene expression. Ingenuity pathway analysis showed the involvement of OPN in functions and networks relevant to angiogenesis, cell death and proliferation of PA-SMC. OPN serum levels did not differ in subjects with Group I PAH and Group II PH.
In the lungs of patients with severe PAH, OPN is highly expressed and the level of expression is significantly correlated to disease severity. OPN may play an important role in the vascular remodelling process of PAH.
骨桥蛋白（OPN）是一种多效细胞因子，参与肺动脉平滑肌细胞（PA-SMC）的增殖。OPN 在与肺纤维化相关的肺动脉高压（PH）患者的肺部上调，这表明肺是 OPN 的来源。我们假设 I 型肺动脉高压（PAH）患者的肺中 OPN 表达升高，并且与血液动力学相关。
从 15 例接受肺移植（LTx）的 I 型 PAH 患者和 11 例正常对照者的肺组织中提取 RNA 后，进行微阵列分析（Affymetrix）。在开始 LTx 之前，术中记录肺动脉压力水平。在右心导管检查当天，测量 PAH 患者、II 型 PH 患者和正常对照者的血清 OPN 水平。
与正常对照者相比，OPN 是 PAH 中上调最多的前五名基因之一，这通过逆转录聚合酶链反应（RT-PCR）得到了证实。PAH 的不同亚型中 OPN 的表达相似且同样升高。平均肺动脉压与 OPN 基因表达之间存在强烈的显著相关性。Ingenuity 通路分析表明 OPN 参与与血管生成、PA-SMC 死亡和增殖相关的功能和网络。I 型 PAH 和 II 型 PH 患者的 OPN 血清水平无差异。
在严重 PAH 患者的肺部，OPN 高表达，表达水平与疾病严重程度显著相关。OPN 可能在 PAH 的血管重塑过程中发挥重要作用。
