Show simple item record

AuthorOsman, Aisha
AuthorEl-Gamal, Heba
AuthorPasha, Mazhar
AuthorZeidan, Asad
AuthorKorashy, Hesham M
AuthorAbdelsalam, Shahenda S
AuthorHasan, Maram
AuthorBenameur, Tarek
AuthorAgouni, Abdelali
Available date2021-01-13T08:15:49Z
Publication Date2020-12-10
Publication NameFrontiers in Cardiovascular Medicine
Identifierhttp://dx.doi.org/10.3389/fcvm.2020.584791
CitationOsman A, El-Gamal H, Pasha M, Zeidan A, Korashy HM, Abdelsalam SS, Hasan M, Benameur T, Agouni A. Endoplasmic Reticulum (ER) Stress-Generated Extracellular Vesicles (Microparticles) Self-Perpetuate ER Stress and Mediate Endothelial Cell Dysfunction Independently of Cell Survival. Front Cardiovasc Med. 2020 Dec 10;7:584791. doi: 10.3389/fcvm.2020.584791. PMID: 33363219; PMCID: PMC7758248.
URIhttp://hdl.handle.net/10576/17303
AbstractCirculating extracellular vesicles (EVs) are recognized as biomarkers and effectors of endothelial dysfunction, the initiating step of cardiovascular abnormalities. Among these EVs, microparticles (MPs) are vesicles directly released from the cytoplasmic membrane of activated cells. MPs were shown to induce endothelial dysfunction through the activation of endoplasmic reticulum (ER) stress. However, it is not known whether ER stress can lead to MPs release from endothelial cells and what biological messages are carried by these MPs. Therefore, we aimed to assess the impact of ER stress on MPs shedding from endothelial cells, and to investigate their effects on endothelial cell function. EA.hy926 endothelial cells or human umbilical vein endothelial cells (HUVECs) were treated for 24 h with ER stress inducers, thapsigargin or dithiothreitol (DTT), in the presence or absence of 4-Phenylbutyric acid (PBA), a chemical chaperone to inhibit ER stress. Then, MPs were isolated and used to treat cells (10-20 μg/mL) for 24-48 h before assessing ER stress response, angiogenic capacity, nitric oxide (NO) release, autophagy and apoptosis. ER stress (thapsigargin or DDT)-generated MPs did not differ quantitatively from controls; however, they carried deleterious messages for endothelial function. Exposure of endothelial cells to ER stress-generated MPs increased mRNA and protein expression of key ER stress markers, indicating a vicious circle activation of ER stress. ER stress (thapsigargin)-generated MPs impaired the angiogenic capacity of HUVECs and reduced NO release, indicating an impaired endothelial function. While ER stress (thapsigargin)-generated MPs altered the release of inflammatory cytokines, they did not, however, affect autophagy or apoptosis in HUVECs. This work enhances the general understanding of the deleterious effects carried out by MPs in medical conditions where ER stress is sustainably activated such as diabetes and metabolic syndrome.
Languageen
PublisherFrontiers Media
SubjectER stress
apoptosis
cardiovascular disease
endothelial function (dysfunction)
extracellular vesicles (EVs)
microparticles (MPs)
TitleEndoplasmic Reticulum (ER) Stress-Generated Extracellular Vesicles (Microparticles) Self-Perpetuate ER Stress and Mediate Endothelial Cell Dysfunction Independently of Cell Survival.
TypeArticle
Volume Number7
ESSN2297-055X
dc.accessType Open Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record