Increased circulating CD31+/CD42b-EMPs in Perthes disease and inhibit HUVECs angiogenesis via endothelial dysfunction

• Published in: Life sciences (1973) 2021-01, Vol.265, p.118749-118749, Article 118749
• Main Authors: Li, Boxiang, Huang, Qian, Lin, Chengsen, Lu, Rongbin, Wang, Tiantian, Chen, Xianxiang, Liu, Zhengtang, Liu, Yun, Wu, Jianping, Wu, Yang, Liao, Shijie, Ding, Xiaofei
• Format: Article
• Language: English
• Subjects: Angiogenesis; Apoptosis; Apoptosis - physiology; Biomarkers; Biomarkers - metabolism; Case-Control Studies; Cell-Derived Microparticles - metabolism; Cell-Derived Microparticles - pathology; Child; Child, Preschool; Endothelial cells; Endothelial Cells - immunology; Endothelial Cells - pathology; Endothelial dysfunction; Endothelial microparticles; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Extracellular Vesicles - immunology; Extracellular Vesicles - pathology; Female; Flow cytometry; Flow Cytometry - methods; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Interleukin 6; Ischemic necrosis of the femoral head; Legg-Calve-Perthes Disease - blood; Legg-Calve-Perthes Disease - immunology; Legg-Calve-Perthes Disease - pathology; Legg-Calvé-Perthes disease; Male; Microparticles; Neovascularization, Pathologic - immunology; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Nitric oxide; Osteochondrosis; Phenotype; Phenotypes; Umbilical vein; Vascular Diseases - metabolism; Vascular Diseases - pathology
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118749

Endothelial microparticles (EMPs) are extracellular vesicles secreted by endothelial cells. The purpose of this research is to explore that the clinical significance and roles in angiogenesis and endothelial dysfunction of circulating microparticles in Perthes disease. We collected platelet-poor plasma (PPP) from patients and controls, then microparticles (MPs) were extracted. Flow cytometry was performed to calculate the concentrations of CD31+/CD42b-, CD62E+ and CD31+/CD42b+ MPs. ELISA was performed to detect the expression level of biomarkers of endothelial dysfunction and inflammatory factors in plasma. In vitro experiments to evaluate the effect of circulating MPs and EMPs derived from IL-6-stimulated human umbilical vein endothelial cells (HUVECs) on angiogenesis and endothelial dysfunction. Our results revealed that the CD31+/CD42b- EMPs were significantly higher in Perthes disease group than in the control group. The Perthes-MPs being taken up by HUVECs promoted endothelial cell apoptosis, endothelial dysfunction and inhibited angiogenesis in vitro. Moreover, the level of IL-6 in plasma significantly increased in patients with Perthes, which was tightly correlated with the elevated level of circulating CD31+/CD42b- EMPs. IL-6 promoted HUVECs to secrete CD31+/CD42b- MPs, and EMPs derived from high concentration IL-6-stimulated (100 and 1000 pg/mL) HUVECs promoted endothelial cell apoptosis, endothelial dysfunction and inhibited angiogenesis. In summary, our study suggests that circulating EMPs in the phenotypic spectrum revealed unique phenotypes of endothelial dysfunction, showing close correlation with the secretion of IL-6. These circulating EMPs may give rise to endothelial cell apoptosis, endothelial dysfunction and angiogenesis in Perthes disease.