Conclusion
Our results suggest that STS enhances maintenance of mitochondrial homeostasis and inhibits mitochondrial ROS overproduction via AMPK, thereby improving endothelial cell pyroptosis during AS.
Purpose
In this study, we investigated whether STS plays a protective role in AS by regulating endothelial cell mitochondrial function and pyroptosis through an AMPK-dependent mitochondrial pathway.
Results
Male ApoE-/- mice and HUVECs were used for the experiments. We found that STS treatment largely abrogated the upregulation of key proteins in aortic vessel wall plaques and typical pyroptosis signaling in ApoE-/- mice fed a western diet, consequently enhancing pAMPK expression, plaque stabilization, and anti-inflammatory responses. Consistently, STS pretreatment inhibited cholesterol crystallization (CC) -induced cell pyroptosis and activated pAMPK expression. In vitro, using HUVECs, we further found that STS treatment ameliorated mitochondrial ROS caused by CC, as evidenced by the finding that STS inhibited mitochondrial damage caused by CC. The improvement of endothelial cell mitochondrial function by STS is blocked by dorsomorphin (AMPK inhibitor). Consistently, the blockade of endothelial cell pyroptosis by STS is disrupted by dorsomorphin.