a Department of Cardiology , Medical University of Bialystok , Bialystok , Poland.
b Department of Cardiology , Cardinal Wyszynski Hospital , Lublin , Poland.
Platelets. 2019;30(4):445-451. doi: 10.1080/09537104.2018.1457780. Epub 2018 Apr 4.
Inflammatory processes and platelet activity play an important role in the pathophysiology of pulmonary arterial hypertension (PAH). Enhanced IL-6 signaling and higher concentration of stromal-derived factor alpha (SDF-1) have been previously shown to be linked with prognosis in PAH. We hypothesized that platelets of PAH patients have higher content of IL-6 and SDF-1 and thus are involved in disease progression. We enrolled into study 22 PAH patients and 18 healthy controls. Patients with PAH presented significantly higher plasma concentrations and platelet contents of IL-6, sIL-6R, and SDF-1 than healthy subjects (platelet content normalized to protein concentration: IL-6 (0.8510 [0.29 - 1.37] vs. 0.4510 [0.19-0.65], sIL-6R 1.5410 [1.32-2.21] vs. 1.1410 [1.01-1.28] and SDF-1 (2.7210 [1.85-3.23] vs. 1.7010 [1.43-2.60], all p < 0.05). Patients with disease progression (death, WHO class worsening, or therapy escalation, n = 10) had a significantly higher platelet SDF-1/total platelet protein ratio (3.6810 [2.45-4.62] vs. 1.6910 [1.04-2.28], p = 0.001), with no significant differences between plasma levels. Kaplan-Meier analysis revealed that patients with higher platelet SDF-1/total platelet protein ratio had more frequently deterioration of PAH in the follow-up (15.24 ± 4.26 months, log-rank test, p = 0.01). Concentrations of IL-6, sIL-6 receptor and SDF-1 in plasma and platelets are elevated in PAH patients. Higher content of SDF-1 in platelets is associated with poorer prognosis. Our study, despite of limitation due to small number of enrolled patients, suggests that activated platelets may be an important source of cytokines at the site of endothelial injury, but their exact role in the pathogenesis of PAH requires further investigation.
在肺动脉高压（PAH）的病理生理学中，炎症过程和血小板活性起着重要作用。先前已经表明，白细胞介素 6（IL-6）信号增强和基质衍生因子 alpha（SDF-1）浓度较高与 PAH 的预后相关。我们假设 PAH 患者的血小板中含有更高水平的 IL-6 和 SDF-1，因此参与了疾病的进展。我们招募了 22 名 PAH 患者和 18 名健康对照者。与健康受试者相比，PAH 患者的血浆浓度和血小板中 IL-6、sIL-6R 和 SDF-1 的含量明显更高（以蛋白浓度标准化的血小板含量：IL-6（0.8510 [0.29-1.37] vs. 0.4510 [0.19-0.65]，sIL-6R 1.5410 [1.32-2.21] vs. 1.1410 [1.01-1.28]和 SDF-1（2.7210 [1.85-3.23] vs. 1.7010 [1.43-2.60]，所有 p 值均 < 0.05）。病情进展（死亡、WHO 功能分级恶化或治疗升级，n=10）的患者血小板 SDF-1/总血小板蛋白比值明显更高（3.6810 [2.45-4.62] vs. 1.6910 [1.04-2.28]，p=0.001），而血浆水平无显著差异。Kaplan-Meier 分析显示，血小板 SDF-1/总血小板蛋白比值较高的患者在随访中更频繁地出现 PAH 恶化（15.24±4.26 个月，对数秩检验，p=0.01）。PAH 患者的血浆和血小板中白细胞介素 6（IL-6）、sIL-6 受体和 SDF-1 浓度升高。血小板中 SDF-1 的含量较高与预后较差相关。尽管由于纳入患者数量有限，我们的研究存在一定局限性，但我们的研究表明，活化的血小板可能是内皮损伤部位细胞因子的重要来源，但它们在 PAH 发病机制中的确切作用还需要进一步研究。
