Knockdown of VAMP8 attenuates atherosclerosis and enhances the effect of simvastatin in APOE-deficient mice

Purpose: To investigate the regulatory effects of vesicle-associated membrane protein 8 (VAMP8) in atherosclerosis (AS). Methods: VAMP8 expression was assessed using quantitative real time-polymerase chain reaction (qRT-PCR) and western blot, while H&E staining was used to examine the morphology of arterial glandular tissues in AS mice. Lipid accumulation in mice was determined with the aid of Oil Red O staining, whereas the apoptosis of aortic cells was evaluated by TUNEL assay. Results: VAMP8 was highly expressed in the advanced-stage AS samples, and was also elevated in AS mice (p < 0.01). VAMP8 protein level rose in AS mice (p < 0.01). Moreover, the aorta showed atherosclerotic lesions with intima thickening and atherosclerotic plaques in AS group (p < 0.01). However, these changes were alleviated in VAMP8-silenced group (p < 0.01). VAMP8 silencing decreased lipid accumulation and alleviated inflammation and oxidative stress in AS mice (p < 0.01). It was observed that depletion of VAMP8 reduced aortic cell apoptosis in AS mice (p < 0.05). Furthermore, VAMP8 knockdown enhanced the effect of simvastatin on atherosclerosis (p < 0.01). Conclusion: Knockdown of VAMP8 alleviates AS in ApoE-deficient mice. This finding suggests that this might be a potential strategy for the prevention and treatment of AS.