The Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road, Guangzhou, Guangdong Province, China.
Department of Critical Care Medicine, The Seventh Affiliated Hospital of Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, Guangdong Province, China.
Biomed Res Int. 2018 Jun 10;2018:3261436. doi: 10.1155/2018/3261436. eCollection 2018.
Chronic obstructive pulmonary disease (COPD) is one of the common and underdiagnosed diseases with the highest morbidity and mortality in the world. The development of COPD can lead to pulmonary vascular remodeling and pulmonary hypertension, further causing the occurrence of pulmonary heart disease. Therefore, attenuation of pulmonary vascular remodeling and pulmonary hypertension caused by COPD can significantly delay cardiovascular complications. In the study, we firstly found that the expression of CD30 and CD30L was increased in COPD. Importantly, the serum CD30L levels were significantly higher in patients with stable COPD relative to those with acute exacerbation of COPD (AECOPD). This suggested that CD30 might be related to the development of COPD. In addition, we found that the expression of CD30 in the COPD rat model was significantly increased compared with control group. And treatment with the anti-CD30 antibody reduced the serum concentration and tissue expression of CD30 in rat. Importantly, anti-CD30 antibody alleviated pulmonary vascular remodeling in COPD model rats. This suggested that CD30 played an important role in the course of COPD. Finally, we found that, in the HPASMC and HPAEC cell lines, CD30 can affect the cell viability and cell migration and inhibited hypoxia-induced cell apoptosis in a concentration-dependent manner. We also found CD30 induced extracellular matrix formation through decreasing the expression of MMP-2, thus promoting the pulmonary vascular remodeling. The study indicated that CD30 and CD30L were involved in pulmonary vascular remodeling and inflammatory response in COPD. Altogether, CD30 might be a marker for the early diagnosis and progression of COPD.
慢性阻塞性肺疾病(COPD)是世界上发病率和死亡率最高的常见且未被充分诊断的疾病之一。COPD 的发展可导致肺血管重塑和肺动脉高压,进而导致肺心病的发生。因此,减轻 COPD 引起的肺血管重塑和肺动脉高压可以显著延缓心血管并发症的发生。在本研究中,我们首先发现 CD30 和 CD30L 的表达在 COPD 中增加。重要的是,与 AECOPD 患者相比,稳定期 COPD 患者的血清 CD30L 水平显著升高。这表明 CD30 可能与 COPD 的发生有关。此外,我们发现 COPD 大鼠模型中 CD30 的表达明显高于对照组。并且用抗 CD30 抗体治疗可降低大鼠血清中 CD30 的浓度和组织表达。重要的是,抗 CD30 抗体减轻了 COPD 模型大鼠的肺血管重塑。这表明 CD30 在 COPD 病程中发挥了重要作用。最后,我们发现,在 HPASMC 和 HPAEC 细胞系中,CD30 可以以浓度依赖的方式影响细胞活力和细胞迁移,并抑制缺氧诱导的细胞凋亡。我们还发现 CD30 通过降低 MMP-2 的表达诱导细胞外基质形成,从而促进肺血管重塑。研究表明 CD30 和 CD30L 参与 COPD 中的肺血管重塑和炎症反应。总的来说,CD30 可能是 COPD 早期诊断和进展的标志物。