Iron supplementation prevents abdominal aortic aneurysm by increasing Tregs via maintained mitochondrial homeostasis

Abdominal aortic aneurysm (AAA) is a life-threatening Cardiovascular Disease with few effective treatments. Iron, an essential trace element, influences cellular functional states through multiple pathways and has been implicated in the pathogenesis and development of AAA. Previous studies have associated iron deficiency (ID) with the phenotypic switching of vascular smooth muscle cells by affecting mitochondrial and endoplasmic reticulum function. In this study, we demonstrate the protective role of appropriate iron supplementation in the progression of AAA. Our data further showed that iron supplementation increases the abundance of regulatory T cells (Tregs) both in the peripheral immune system and in aortic tissues, contributing to its protective effect. Moreover, iron supplementation inhibits the expression of mitochondrial uncoupling protein 2 (UCP2) in Tregs, which in turn suppresses the phosphorylation of dynamin-related protein 1 (Drp1), thereby modulating the dynamic balance between mitochondrial fusion and fission. Our findings suggest that iron supplementation may serve as a potential intervention to delay and ameliorate the progression of AAA.