Disruption of the novel nested gene <i>Aff3ir</i> mediates disturbed flow-induced atherosclerosis in mice.

ABSTRACT: Disturbed shear stress-induced endothelial atherogenic responses are pivotal in the initiation and progression of atherosclerosis, contributing to the uneven distribution of atherosclerotic lesions. This study investigates the role of Aff3ir-ORF2, a novel nested gene variant, in disturbed flow-induced endothelial cell activation and atherosclerosis. We demonstrate that disturbed shear stress significantly reduces Aff3ir-ORF2 expression in athero-prone regions. Using three distinct mouse models with manipulated Aff3ir-ORF2 expression, we demonstrate that Aff3ir-ORF2 exerts potent anti-inflammatory and anti-atherosclerotic effects in Apoe^-/- mice. RNA sequencing revealed that interferon regulatory factor 5 (Irf5), a key regulator of inflam

SUBMITTER: He S 

PROVIDER: S-EPMC12048156 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature