Targeting α7nAChR mitigates vascular aging and endothelial cell senescence through inhibiting oxidative stress and inflammation via α7nAChR/Nrf2/HO-1 signaling pathway

Vascular aging is recognized as critical factor contributing to the onset and progression of cardiovascular diseases, which represent a leading cause of morbidity and mortality worldwide. The α7 nicotinic acetylcholine receptor (α7nAChR) exhibits widespread expressed in the cardiovascular system and is intricately linked to a diverse array of pathologies, in cardiovascular, conditions. Research indicates that oxidative stress plays a crucial role in exacerbating endothelial dysfunction and promoting vascular aging. However, less is known regarding the role of α7nAChR in vascular aging. In this study, we employed a combination of cellular experiments, animal models, and molecular biological techniques, utilizing an agonist (PNU282987) and antagonists (Malondialdehyde, MLA) of α7nAChR as pharmacological tools to investigate the role of α7nAChR in aging-related pathologies. The expression of α7nAChR in vascular tissue decreases with age both in rats and humans. Activation of α7nAChR alleviated vascular aging in aged rats, as evidenced by improving endothelium-dependent vasodilatation and endothelial continuity, decreased senescence-associated β-galactosidase activity, phosphorylation of H2A.XSer139, expression of p21 and p16INK4a and inflammation, Notably, effective activation of the α7nAChR mediated Nrf2/HO-1 signaling pathway and antioxidant activity by specific agonist, PNU282987, conversely, which were blocked by the α7nAChR-selective inhibitor MLA. The findings highlight the vital role of α7nAChR receptor in preserving vascular health and endothelial integrity in the development of vascular aging, Consequently, targeting the α7nAChR/Nrf2/HO-1 signaling pathway could serve as a potential therapeutic approach for the development of novel anti-aging strategies.