Waschki Benjamin, Watz Henrik, Holz Olaf, Magnussen Helgo, Olejnicka Beata, Welte Tobias, Rabe Klaus F, Janciauskiene Sabina
Pneumology, LungenClinic Grosshansdorf, Grosshansdorf, Germany; Pulmonary Research Institute at LungenClinic Grosshansdorf, Grosshansdorf, Germany; Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany.
Pulmonary Research Institute at LungenClinic Grosshansdorf, Grosshansdorf, Germany; Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany.
Int J Chron Obstruct Pulmon Dis. 2017 Mar 22;12:981-987. doi: 10.2147/COPD.S128689. eCollection 2017.
Plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of fibrinolysis, is associated with thrombosis, obesity, insulin resistance, dyslipidemia, and premature aging, which all are coexisting conditions of chronic obstructive pulmonary disease (COPD). The role of PAI-1 in COPD with respect to metabolic and cardiovascular functions is unclear.
In this study, which was nested within a prospective cohort study, the serum levels of PAI-1 were cross-sectionally measured in 74 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I-IV) and 18 controls without lung disease. In addition, triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, waist circumference, blood pressure, smoking status, high-sensitive C-reactive protein (hs-CRP), adiponectin, ankle-brachial index, N-terminal pro-B-type natriuretic peptide, and history of comorbidities were also determined.
The serum levels of PAI-1 were significantly higher in COPD patients than in controls, independent of a broad spectrum of possible confounders including metabolic and cardiovascular dysfunction. A multivariate regression analysis revealed triglyceride and hs-CRP levels to be the best predictors of PAI-1 within COPD. GOLD Stages II and III remained independently associated with higher PAI-1 levels in a final regression analysis.
The data from the present study showed that the serum levels of PAI-1 are higher in patients with COPD and that moderate-to-severe airflow limitation, hypertriglyceridemia, and systemic inflammation are independent predictors of an elevated PAI-1 level. PAI-1 may be a potential biomarker candidate for COPD-specific and extra-pulmonary manifestations.
纤溶酶原激活物抑制剂-1(PAI-1)是纤维蛋白溶解的主要抑制剂,与血栓形成、肥胖、胰岛素抵抗、血脂异常和早衰相关,而这些都是慢性阻塞性肺疾病(COPD)的共存病症。PAI-1在COPD中关于代谢和心血管功能的作用尚不清楚。
在这项嵌套于前瞻性队列研究中的研究中,对74例稳定期COPD患者(慢性阻塞性肺疾病全球倡议组织[GOLD] I-IV级)和18例无肺部疾病的对照者进行了PAI-1血清水平的横断面测量。此外,还测定了甘油三酯、高密度脂蛋白胆固醇、空腹血糖、腰围、血压、吸烟状况、高敏C反应蛋白(hs-CRP)、脂联素、踝臂指数、N末端B型脑钠肽前体以及合并症病史。
COPD患者的PAI-1血清水平显著高于对照者,且不受包括代谢和心血管功能障碍在内的广泛潜在混杂因素影响。多变量回归分析显示,甘油三酯和hs-CRP水平是COPD患者中PAI-1的最佳预测指标。在最终回归分析中,GOLD II级和III级仍与较高的PAI-1水平独立相关。
本研究数据表明,COPD患者的PAI-1血清水平较高,且中重度气流受限、高甘油三酯血症和全身炎症是PAI-1水平升高的独立预测因素。PAI-1可能是COPD特异性和肺外表现的潜在生物标志物候选物。