Senescent HUVECs-secreted exosomes trigger endothelial barrier dysfunction in young endothelial cells

Authors

  • Pooi-Fong Wong Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Tel: +603-7967 7022 (ext 2065); Fax: +603-7967 4791, E-mail: wongpf@um.edu.my
  • King-Leng Tong Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • Juliana Jamal Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • Eng-Soon Khor Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • Siew-Li Lai Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • Mohd Rais Mustafa Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

DOI:

https://doi.org/10.17179/excli2019-1505

Keywords:

microvesicular, extracellular vesicle, senescent-associated secretory phenotype (SASP), endothelial adherens junction proteins, senescent HUVECs-secreted exosomes, endothelial barrier dysfunction

Abstract

Accumulation of senescent endothelial cells can cause endothelium dysfunction which eventually leads to age-related vascular disorders. The senescent-associated secretory phenotype (SASP) cells secrete a plethora of soluble factors that negatively influence the surrounding tissue microenvironment. The present study sought to investigate the effects of exosomes, which are nano-sized extracellular vesicles known for intercellular communications secreted by SASP cells on young endothelial cells. Exosomes were isolated from the condition media of senescent human umbilical vein endothelial cells (HUVECs) and then confirmed by the detection of exosome specific CD63 and CD9 expressions, electron microscopy and acetylcholinesterase assay. The purified exosomes were used to treat young HUVECs. Exposure to exosomes repressed the expression of adherens junction proteins including vascular endothelial (VE)-cadherin and beta-catenin, decreased cell growth kinetics and impaired endothelial migration potential of young endothelial cells. These findings suggest that senescent HUVECs-secreted exosomes could disrupt barrier integrity that underpins endothelial barrier dysfunction in healthy young endothelial cells.

Published

2019-09-03

How to Cite

Wong, P.-F., Tong, K.-L., Jamal, J., Khor, E.-S., Lai, S.-L., & Mustafa, M. R. (2019). Senescent HUVECs-secreted exosomes trigger endothelial barrier dysfunction in young endothelial cells. EXCLI Journal, 18, 764–776. https://doi.org/10.17179/excli2019-1505

Issue

Section

Original articles

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