English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Endoplasmic reticulum (ER) stress has been implicated in vascular endothelial dysfunction of obesity, diabetes, and hypertension. MicroRNAs play an important role in regulating ER stress. Here we show that microRNA-204 (miR-204) promotes vascular ER stress and endothelial dysfunction by targeting the Sirtuin1 (Sirt1) lysine deacetylase. Pharmacologic ER stress induced by tunicamycin upregulates miR-204 and downregulates Sirt1 in the vascular wall/endothelium  in vivo  and in endothelial cells  in vitro . Inhibition of miR-204 protects against tunicamycin-induced vascular/endothelial ER stress, associated impairment of endothelium-dependent vasorelaxation, and preserves endothelial Sirt1. A miR-204 mimic leads to ER stress and downregulates Sirt1 in endothelial cells. Knockdown of Sirt1 in endothelial cells, and conditional deletion of endothelial Sirt1 in mice, promotes ER stress via upregulation of miR-204, whereas overexpression of Sirt1 in endothelial cells suppresses miR-204-induced ER stress. Furthermore, increase in vascular reactive oxygen species induced by ER stress is mitigated by by miR-204 inhibition. Finally, nutritional stress in the form of a Western diet promotes vascular ER stress through miR-204. These findings show that miR-204 is obligatory for vascular ER stress and ER stress-induced vascular endothelial dysfunction, and that miR-204 promotes vascular ER stress via downregulation of Sirt1.

MicroRNA-204 promotes vascular endoplasmic reticulum stress and endothelial dysfunction by targeting Sirtuin1