Protective Effects of Pasteurized Akkermansia muciniphila on Ox-LDL-Induced Cell Injury in Human Aortic Endothelial Cells and Underlying Mechanisms

Objective: In this study, pasteurized Akkermansia muciniphila (PAKK) was examined for its protective effect on oxidized low-density lipoprotein (ox-LDL)-induced injury in human aortic endothelial cells (HAEC). Methods: MTT method was used to evaluate the effect of PAKK on HAEC activity and determine the appropriate dose. A model of ox-LDL-induced cell injury was established, and the protective effect of PAKK on HAEC cell injury was evaluated by measuring lactate dehydrogenase and reactive oxygen species. By measuring the activities of antioxidant enzymes and the expression of genes and proteins related to the Nrf2 antioxidant pathway, the possible mechanisms by which PAKK ameliorated HAEC oxidative damage was discussed. Results: PAKK at the doses of 10⁵ and 10⁶ CFU/mL did not affect the viability of HAEC, but significantly reduced the release rate of lactate dehydrogenase induced by ox-LDL. The reactive oxygen species level was decreased, while the activity of superoxide dismutase, catalase and the total antioxidant capacity of cells were significantly increased. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), glutathione S-transferase (GST) and NADPH quinone oxidoreductase-1 (NQO1) were significantly up-regulated. Nrf2, HO-1 and NQO1 protein expression were also significantly enhanced. Conclusion: These findings indicated that PAKK could alleviate the injury of HAEC caused by ox-LDL, and its protective effect was partly mediated through enhanced expression of antioxidant related enzymes by regulating Nrf2 signaling pathway. This study would provide theoretical basis for development of Akkermansia muciniphila-based probiotic or postbiotic for prevention of atherosclerosis.