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Published on: June 8, 2019
Increased circulating CD31+/CD42b-EMPs in Perthes disease and inhibit HUVECs angiogenesis via endothelial dysfunction
Boxiang Li1, Qian Huang1, Chengsen Lin1
1Department of Trauma Orthopedic and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Aims:
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.
Main Methods:
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.
Key Findings:
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.
Significance:
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.
Insights
Circulating endothelial microparticles (EMPs) are elevated in Perthes disease and contribute to endothelial dysfunction and impaired angiogenesis. Interleukin-6 (IL-6) drives EMP production, exacerbating these effects.
Area of Science:
- Vascular Biology
- Pediatric Orthopedics
- Cellular Biology
Background:
- Endothelial microparticles (EMPs) are vesicles released by endothelial cells.
- Perthes disease is a hip disorder affecting children, characterized by compromised blood supply to the femoral head.
- Endothelial dysfunction and impaired angiogenesis are implicated in the pathogenesis of Perthes disease.
Purpose of the Study:
- To investigate the clinical significance of circulating microparticles in Perthes disease.
- To explore the roles of these microparticles in angiogenesis and endothelial dysfunction.
- To determine the relationship between EMPs, Interleukin-6 (IL-6), and disease progression.
Main Methods:
- Plasma samples were collected from Perthes disease patients and controls.
- Flow cytometry quantified specific microparticle populations (CD31+/CD42b-, CD62E+, CD31+/CD42b+).
- ELISA measured biomarkers of endothelial dysfunction and inflammation (IL-6); in vitro assays assessed microparticle effects on human umbilical vein endothelial cells (HUVECs).
Main Results:
- Patients with Perthes disease exhibited significantly higher concentrations of CD31+/CD42b- EMPs compared to controls.
- Perthes disease-derived microparticles induced apoptosis, endothelial dysfunction, and inhibited angiogenesis in HUVECs.
- Elevated plasma IL-6 levels in Perthes disease correlated with increased CD31+/CD42b- EMPs; IL-6 stimulation of HUVECs increased EMP secretion, which in turn impaired endothelial function and angiogenesis.
Conclusions:
- Circulating EMPs in Perthes disease display distinct phenotypes associated with endothelial dysfunction and correlate with IL-6 levels.
- These EMPs contribute to endothelial cell apoptosis, endothelial dysfunction, and angiogenesis inhibition in Perthes disease.
- EMPs represent a potential diagnostic and therapeutic target in Perthes disease management.
