Angiotensin II-induced vascular endothelial cells ferroptosis via P53-ALOX12 signal axis.

Objectives: The present study aimed to investigate the effect and mechanism of angiotensin II-induced ferroptosis in vascular endothelial cells.

Methods: In vitro, HUVECs were treated with AngII, AT R antagonist, P53 inhibitor, or their combinations. MDA and intracellular iron content were evaluated using an ELISA assay. The expression of ALOX12, P53, P21, and SLC7A11 were determined by western blotting in HUVECs and then confirmed through RT-PCR.

Results: As the concentration of Ang II (0, 0.1,1,10,100, and 1000uM for 48 h) increased, the level of MDA and intracellular iron content increased in HUVECs. Compared with the single AngII group, ALOX12, p53, MDA, and intracellular iron content in ATR antagonist group decreased significantly. In pifithrin-α hydrobromide-treated, ALOX12, P21,MDA, and intracellular iron content decreased significantly as compared to the single AngII group. Similarly, the effect of combined use of blockers is stronger than that of blockers alone.

Conclusions: AngII can induce ferroptosis of vascular endothelial cells. The mechanism of AngII-induced ferroptosis may be regulated through the signal axis of p53-ALOX12.