Aim: Smoking is a major risk factor for
abdominal aortic aneurysm (AAA). Among the components of
smoke,
nicotine is known to exert pro-atherosclerotic, prothrombotic, and proangiogenic effects on vascular smooth muscle cells (VSMCs). The current study was designed to investigate the mechanisms through which
nicotine induces vascular wall dysfunction and to examine whether
melatonin protects against
nicotine-related AAA. Methods: In this study, an
enzyme-linked
immunosorbent assay (ELISA) was used to measure
melatonin and TNF-α levels, as well as total
antioxidant status (TAS), in patients with AAA. We established a
nicotine-related AAA model and explored the mechanisms underlying the
therapeutic effects of
melatonin. Tissue histopathology was used to assess vascular function, while western blotting (WB) and immunofluorescence staining were performed to detect
protein expression. Results: We observed
melatonin insufficiency in the serum from patients with AAA, particularly smokers. Moreover,
melatonin level was positively correlated with
antioxidant capacity. In the in vivo model,
nicotine accelerated AAA expansion and destroyed vascular structure. Furthermore, OPN, LC3II, p62,
matrix metalloproteinase-2 (MMP-2),
matrix metalloproteinase-9 (MMP-9), NF-κB p65, TNF-α, phosphorylated AKT, and phosphorylated mTOR levels were increased, in vivo, following
nicotine treatment, while SM22α and α-SMA levels were reduced. Additionally,
melatonin attenuated the effects of
nicotine on AAA and reversed changes in
protein expression. Moreover,
melatonin lost its protective effects following bafilomycin A1-mediated inhibition of autophagy. Conclusion: Based on our data,
melatonin exerts a beneficial effect on rats with
nicotine-related AAA by downregulating the AKT-mTOR signaling pathway, improving autophagy dysfunction, and restoring the VSMC phenotype.