ABI3BP deficiency alleviates Ang II-induced VSMC senescence through the Nrf2 signalling pathway

Vascular aging is a critical independent risk factor for cardiovascular disease (CVD), yet its precise molecular mechanisms remain poorly understood. In this study, we generated an ABI3BP knockout mouse to investigate the role of ABI3BP deficiency in angiotensin II (Ang II)-induced vascular aging. The results demonstrated that ABI3BP was highly expressed in AngII-induced senescent vascular smooth muscle cell (VSMC) and vascular tissues, with significantly increased expression also observed in the blood vessels of naturally aged mice. Downregulation of ABI3BP expression using siRNA significantly inhibited Ang II-induced senescence of VSMC. ABI3BP knockout ameliorated Ang II-induced vascular aging in mice, reduced the secretion of senescence-associated inflammatory factors IL-6 and TNF-α, alleviated senescence-induced accumulation of collagen in the vascular media and thickening of the vascular intima, and effectively suppressed Ang II-induced elevation of blood pressure. Further investigations revealed that these protective effects might be mediated through enhanced expression of Nrf2 and its downstream anti-aging factors. Silencing Nrf2 with siRNA attenuated the protective effects of ABI3BP downregulation on vascular aging. Overall, these findings demonstrate that ABI3BP downregulation inhibits VSMC senescence by enhancing the activity of the Nrf2-mediated antioxidant defense pathway, thereby attenuating the progression of vascular aging.