Objective: To investigate effect of oleanolic acid (OA) on atherosclerosis and its related mechanisms.
Methods: Human umbilical vein endothelial cells (HUVECs) were injured by oxidized low-density lipoprotein for 24 h and treated with OA, and the levels of cell proliferation, migration, adhesion, and apoptosis were evaluated by BrdU staining, scratch healing assay, monocyte-endothelial cell adhesion assay and flow cytometry. The mice were fed with a high-fat diet to induce an atherosclerosis model, and treated with OA by gastric gavage. The mice were divided into the control group, the model group, and the OA administration group. The blood lipid and plaque formation in mice were detected. In addition, oxidative stress and mitochondrial structure and function changes in cells and mice were evaluated by transmission electron microscopy, JC-1 fluorescent probe, and Western blotting assays. The expression levels of proteins in the AMPK/Drp1 pathway were examined through Western blot.
Results: OA markedly increased cell viability and migration rate of HUVECs, and decreased the adhesion rate of THP-1 cells and the apoptosis rate. OA significantly reduced serum lipid levels, such as total cholesterol and triglyceride, in mice and inhibited plaque formation in the aorta. OA also significantly increased the content of superoxide dismutase and catalase, alleviated mitochondrial damage, such as mitochondrial swelling and mitochondrial cristae reduction, reduced the number of mitochondria, increased adenosine triphosphate content, and significantly reduced p-Drp1 (Ser616)/Drp1, MFF and FIS1 levels, increased p-AMPK/AMPK levels, activated AMPK, and then regulated DRP1 activity.
Conclusions: OA activates AMPK, which in turn regulates the activity of DRP1 to restore normal mitochondrial dynamics and reduce atherosclerosis.
Conflict of interest statement
The authors declare that there is no conflict of interest.
Funding
This study received no extramural funding.
Data availability statement
The data supporting the findings of this study are available from the corresponding author upon request.
Authors’ contributions
JZX developed and planned the study, performed experiments, interpreted results, and edited and refined the manuscript with a focus on critical intellectual contributions. WJC and WTZ participated in collecting, assessing, and interpreting the data, and manuscript preparation. LN provided substantial intellectual input during the drafting and revision of the manuscript. All authors have read and approved the final version of the manuscript.
Publisher’s note
The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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