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Up-regulation of autophagy by etanercept treatment results in TNF-induced apoptosis reduction in EA.hy926 endothelial cell line


1, 2, 3, 4, 5, 6, 7, 8, 9, 10

 

  1. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  2. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  3. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  4. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  5. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  6. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  7. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  8. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  9. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  10. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy. cristiano.alessandri@uniroma1.it

CER13285
2021 Vol.39, N°3
PI 0606, PF 0611
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PMID: 32896251 [PubMed]

Received: 05/03/2020
Accepted : 01/06/2020
In Press: 03/09/2020
Published: 21/05/2021

Abstract

OBJECTIVES:
Rheumatoid arthritis (RA) is an autoimmune systemic inflammatory disease associated with a high prevalence of atherosclerosis. Endothelial dysfunction has emerged as a potentially valuable prognostic tool in predicting the development of atherosclerosis. Tumour necrosis factor (TNF) is the main cytokine involved in RA pathogenesis, exerting a pro-atherogenic role. TNF-inhibitors are effective treatments in RA, also improving endothelial function. Regarding this, no experimental data are known about the involvement of etanercept. We investigated the contribution of TNF to endothelial dysfunction and the effect of in vitro treatment with etanercept, with a special focus on autophagy and apoptosis pathways.
METHODS:
Autophagy and apoptosis were evaluated by Western blot and flow cytometry in EA.hy926 endothelial cells treated with TNF alone or in combination with etanercept for 24h.
RESULTS:
Blocking autophagy, TNF was able to induce endothelial cell apoptosis. Co-treatment with etanercept reverted this effect, up-regulating the autophagy pathway.
CONCLUSIONS:
Our results confirm the protective role of etanercept, by restoring autophagy on TNF-induced endothelial damage.

Rheumatology Article