Intercepting the Lipid-Induced Integrated Stress Response Reduces Atherosclerosis.

ABSTRACT:

Background

Eukaryotic cells can respond to diverse stimuli by converging at serine-51 phosphorylation on eukaryotic initiation factor 2 alpha (eIF2α) and activate the integrated stress response (ISR). This is a key step in translational control and must be tightly regulated; however, persistent eIF2α phosphorylation is observed in mouse and human atheroma.

Objectives

Potent ISR inhibitors that modulate neurodegenerative disorders have been identified. Here, the authors evaluated the potential benefits of intercepting ISR in a chronic metabolic and inflammatory disease, atherosclerosis.

Methods

The authors investigated ISR's role in lipid-induced inflammasome activation and atherogenesis by taking advantage of 3 different small molecules and the ATP-analog sensitive ki

SUBMITTER: Onat UI 

PROVIDER: S-EPMC6424590 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature