ER-Stress and Senescence Coordinately Promote Endothelial Barrier Dysfunction in Diabetes-Induced Atherosclerosis.

ABSTRACT: Diabetes mellitus is hallmarked by accelerated atherosclerosis, a major cause of mortality among patients with diabetes. Efficient therapies for diabetes-associated atherosclerosis are absent. Accelerated atherosclerosis in diabetic patients is associated with reduced endothelial thrombomodulin (TM) expression and impaired activated protein C (aPC) generation. Here, we directly compared the effects of high glucose and oxidized LDL, revealing that high glucose induced more pronounced responses in regard to maladaptive unfolded protein response (UPR), senescence, and vascular endothelial cell barrier disruption. Ex vivo, diabetic ApoE^-/- mice displayed increased levels of senescence and UPR markers within atherosclerotic lesions compared with nondiabetic ApoE^-/- mice. A

SUBMITTER: Fatima S 

PROVIDER: S-EPMC9323824 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature