Background: Atherosclerosis, which is a form of chronic aortic disease, results from the accumulation and aggregation of oxidized low density lipoprotein LDL in the vessel walls, the development of neointima, the formation of a fibrous cap, and the migration of immune cells to the damaged vascular endothelium. Recent studies have shown that mitochondrial function is closely associated with the development and progression of atherosclerosis. Idebenone functions as an electron carrier and antioxidant, and previous studies have shown that it effectively clears oxygen-free radicals. In the current study, we demonstrate that idebenone could protect against atherosclerosis using apolipoprotein E-deficient mice.
Background: Atherosclerosis, which is a form of chronic aortic disease, results from the accumulation and aggregation of oxidized low density lipoprotein(LDL)in the vessel walls, the development of neointima, the formation of a fibrous cap, and the migration of immune cells to the damaged vascular endothelium. Recent studies have shown that mitochondrial function is closely associated with the development and progression of atherosclerosis. Idebenone functions as an electron carrier and antioxidant, and previous studies have shown that it effectively clears oxygen-free radicals. In the current study, we demonstrate that idebenone could protect against atherosclerosis using apolipoprotein E-deficient mice. Methods: High-fat diet(HFD)and idebenone treatment with apolipoprotein E-deficient mice . A total of 60 mices were randomized into the following four groups: (1) HFD (2) idebenone-low dose (3) idebenone-medium dose and (4) idebenone-high dose for 16 weeks. The HUVECs were pretreated with endothelial cell medium in the presence or absence of 0.2 mM idebenone working solution for 3 h followed by exposure to 10 μM cholesterol for 24 h. Proteomics analysis was performed between the HFD group (n=3) and the high-dose idebenone group (n=3, concentration = 400 mg/kg/d).Results: Compared with the HFD group, Idebenone can suppresses the formation of atherosclerotic plaques and increases the stability of atherosclerotic plaques in apoE-/- mice; Compared with the control group, Idebenone can protects against endothelial cell damage and inhibits the production of mtROS in cholesterol mediated HUVECs; Idebenone could effectively inhibit the development and progression of atherosclerosis and the injury of endothelial cells through the SIRT3-SOD2-mtROS pathway.Conclusions: We showed that idebenone could act as a mitochondrial protective agent during the development and progression of atherosclerosis by inhibiting the activation of NLPR3 via the SIRT3-SOD2-mtROS pathway. Idebenone may be a promising therapy for patients with atherosclerosis in the future, as it can improve mitochondrial dysfunction and inhibit oxidative stress.
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