Silencing IL2RB attenuates abdominal aortic aneurysm-related pathology in experimental models by partially restoring mitochondrial homeostasis

Abdominal aortic aneurysm (AAA) remains a life-threatening vascular disease with limited therapeutic options. The role of interleukin-2 receptor subunit beta (IL2RB) in AAA via mitochondrial dysfunction is unclear. In this study, integrated bioinformatics analyses identified IL2RB as a key gene. In a rat AAA model and angiotensin II-stimulated vascular smooth muscle cells (VSMCs), IL2RB was upregulated and associated with mitochondrial impairment. IL2RB knockdown attenuated aortic dilation, reduced elastic fiber degradation (decreased by 45%), restored adenosine triphosphate (ATP) production (increased by 126.9%), suppressed interleukin-6 (decreased by 49.3%) and tumor necrosis factor-alpha (decreased by 51.8%) release, and decreased malondialdehyde (reduced by 47.7%) and reactive oxygen species (reduced by 38.5%) production in the rat model. In VSMCs, silencing IL2RB rescued angiotensin II-induced ATP depletion, preserved mitochondrial membrane potential, and reduced apoptosis. Mechanistically, IL2RB knockdown downregulated dynamin-related protein 1, and upregulated mitofusin 1 and parkin RBR E3 ubiquitin protein ligase. IL2RB knockdown mitigates AAA progression by restoring mitochondrial homeostasis and suppressing inflammation, identifying IL2RB as a potential therapeutic target for AAA.