Section of Pulmonary/Critical Care and Allergy Immunology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
Comprehensive Pulmonary Hypertension Center-University Medical Center, New Orleans, LA, USA.
Respirology. 2019 Jul;24(7):675-683. doi: 10.1111/resp.13500. Epub 2019 Feb 12.
Endothelial microparticles (EMP) are submicron vesicles released from endothelial cells. We aimed to determine the utility of EMP as biomarkers of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) patients and the pathogenic role of microparticles (MP) in vascular inflammation.
Levels of EMP (CD144+, CD31+, CD62E+ and CD143+) were compared between three groups (10 SSc patients with PAH, 10 SSc patients without pulmonary hypertension (no-PH) and 10 healthy age- and sex-matched controls). Human pulmonary artery endothelial cells (HPAEC) were exposed in vitro to MP obtained from SSc patients or healthy controls, and levels of cytokines and inflammatory adhesion molecules were compared.
CD144+ EMP were significantly higher in the SSc-PAH group compared to either the SSc-no PH or healthy controls (diagnostic accuracy 80%, P = 0.02). Compared to controls, SSc patients had higher CD31+/CD62E+ ratios, indicating larger contributions of apoptosis to EMP release (P = 0.04). Patients with limited SSc had significantly higher levels of CD143+ EMP compared to those with diffuse subtype (P = 0.008). When HPAEC were exposed to MP from SSc patients, there was a significant increase in inflammatory cytokines and adhesion molecules. Interestingly, exposure to healthy control MP caused a reduction in inflammatory markers.
EMP (particularly CD144+) are promising biomarkers of PAH in SSc but require further study. MP isolated from SSc patients induced an increase in endothelial cell inflammation and may be an important pathogenic factor in SSc.
内皮细胞微粒（EMP）是从内皮细胞释放的亚微米囊泡。我们旨在确定 EMP 作为系统性硬皮病（SSc）患者肺动脉高压（PAH）生物标志物的效用，以及微粒（MP）在血管炎症中的致病作用。
比较三组之间的 EMP 水平（CD144+，CD31+，CD62E+和 CD143+）（10 例 SSc 合并 PAH 患者，10 例 SSc 无肺动脉高压（无 PH）患者和 10 例年龄和性别匹配的健康对照者）。体外将 SSc 患者或健康对照者的 MP 暴露于人肺动脉内皮细胞（HPAEC），比较细胞因子和炎症黏附分子的水平。
与 SSc-no PH 或健康对照组相比，SSc-PAH 组的 CD144+ EMP 明显更高（诊断准确性 80%，P=0.02）。与对照组相比，SSc 患者的 CD31+/CD62E+ 比值更高，表明 EMP 释放中凋亡的贡献更大（P=0.04）。局限型 SSc 患者的 CD143+ EMP 水平明显高于弥漫型（P=0.008）。当 HPAEC 暴露于 SSc 患者的 MP 时，炎症细胞因子和黏附分子明显增加。有趣的是，暴露于健康对照者的 MP 导致炎症标志物减少。
EMP（特别是 CD144+）是 SSc 中 PAH 的有前途的生物标志物，但需要进一步研究。从 SSc 患者中分离出的 MP 诱导内皮细胞炎症增加，可能是 SSc 中的一个重要致病因素。
