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Published on: October 16, 2016
TNFα expressed on the surface of microparticles modulates endothelial cell fate in rheumatoid arthritis
Cristiana Barbati1, Marta Vomero2, Tania Colasanti2
1Arthritis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. cristiana.barbati1@gmail.com.
Background:
Rheumatoid arthritis (RA) is associated with a high prevalence of atherosclerosis. Recently increased levels of microparticles (MPs) have been reported in patients with RA. MPs could represent a link between autoimmunity and endothelial dysfunction by expressing tumor necrosis factor alpha (TNFα), a key cytokine involved in the pathogenesis of RA, altering endothelial apoptosis and autophagy. The aim of this study was to investigate TNFα expression on MPs and its relationship with endothelial cell fate.
Methods:
MPs were purified from peripheral blood from 20 healthy controls (HC) and from 20 patients with RA, before (time (T)0) and after (T4) 4-month treatment with etanercept (ETA). Surface expression of TNFα was performed by flow cytometry analysis. EA.hy926 cells, an immortalized endothelial cell line, were treated with RA-MPs purified at T0 and at T4 and also, with RA-MPs in vitro treated with ETA. Apoptosis and autophagy were then evaluated.
Results:
RA-MPs purified at T0 expressed TNFα on their surface and this expression significantly decreased at T4. Moreover, at T0 RA-MPs, significantly increased both apoptosis and autophagy levels on endothelial cells, in a dose-dependent manner. RA-MPs did not significantly change these parameters after 4 months of in vivo treatment with ETA.
Conclusions:
Our data demonstrate that MPs isolated from patients with RA exert a pathological effect on endothelial cells by TNFα expressed on their surface. In vivo and in vitro treatment with ETA modulates this effect, suggesting anti-TNF therapy protects against endothelial damage in patients with RA.
Insights
Microparticles (MPs) from rheumatoid arthritis (RA) patients expressing tumor necrosis factor alpha (TNFα) damage endothelial cells. Anti-TNF therapy, like etanercept (ETA), shows promise in protecting against this RA-associated endothelial damage.
Area of Science:
- Immunology
- Cardiovascular Research
- Cell Biology
Background:
- Rheumatoid arthritis (RA) is linked to increased atherosclerosis and elevated microparticle (MP) levels.
- MPs may bridge autoimmunity and endothelial dysfunction in RA by expressing TNFα, impacting endothelial apoptosis and autophagy.
- Understanding the role of TNFα on MPs is crucial for RA pathogenesis and cardiovascular risk.
Purpose of the Study:
- To investigate TNFα expression on MPs from RA patients.
- To determine the relationship between TNFα-expressing MPs and endothelial cell fate (apoptosis and autophagy).
- To evaluate the impact of etanercept (ETA) treatment on TNFα-expressing MPs and endothelial cells.
Main Methods:
- Purified MPs from 20 RA patients and 20 healthy controls (HC) before (T0) and after (T4) 4-month ETA treatment.
- Flow cytometry assessed surface TNFα expression on MPs.
- Endothelial EA.hy926 cells were treated with RA-MPs (T0 and T4) and in vitro ETA-treated RA-MPs to evaluate apoptosis and autophagy.
Main Results:
- RA-derived MPs (RA-MPs) at T0 showed significant surface TNFα expression, which decreased at T4.
- RA-MPs at T0 dose-dependently increased endothelial cell apoptosis and autophagy.
- In vivo ETA treatment for 4 months did not significantly alter these effects of RA-MPs on endothelial cells.
Conclusions:
- MPs from RA patients, via surface TNFα, exert pathological effects on endothelial cells.
- In vivo and in vitro ETA treatment modulates these effects, indicating anti-TNF therapy's protective potential against endothelial damage in RA.
- Targeting TNFα on MPs may be a therapeutic strategy to mitigate cardiovascular complications in rheumatoid arthritis.
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