NDUFAF2 promotes abdominal aortic aneurysm formation through mitochondrial dysfunction-induced apoptosis.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease closely associated with mitochondrial dysfunction and apoptosis. Here, we found that NDUFAF2 (NADH dehydrogenase (ubiquinone) 1 alpha subcomplex assembly factor 2) was significantly upregulated in cultured cells and murine AAA tissues. Knockdown of NDUFAF2 in vitro attenuated Ang II-induced mitochondrial fragmentation, reactive oxygen species (ROS) production, and apoptosis in vascular smooth muscle cells (VSMCs), while improving mitochondrial membrane potential and oxygen consumption rate. In addition, NDUFAF2 knockdown reduced the expression of DRP1 (dynamin-related protein 1) while restoring the mitochondrial fusion protein OPA1 (optic atrophy 1), and OPA1 overexpression further enhanced mitochondrial integrity and function. In vivo, NDUFAF2 knockdown suppressed CaCl2-induced AAA formation, preserved aortic structure, reduced apoptosis, and restored mitochondrial complex subunits and smooth muscle cell markers. These results indicate that NDUFAF2 contributes to AAA progression by triggering mitochondrial damage and apoptosis, representing a promising therapeutic target for AAA.