FIGURE 4.
p53 mediates Lp(a)-induced cardiomyocyte ferroptosis. (A) Pre-treatment with 10 μmoL/L pifithrin-α for 1 h attenuated Lp(a)-induced upregulation of p53 and ACSL4 as well as downregulation of SLC7A11 and GPX4 in AC16 cells. (B) Pifithrin-α pre-treatment for 1 h suppressed Lp(a)-triggered cardiomyocyte death. (C) Pifithrin-α pre-treatment for 1 h mitigated Lp(a)-induced elevation of FerroOrange fluorescence intensity. (D) Pifithrin-α pre-treatment for 1 h reduced Lp(a)-elevated intracellular MDA levels. (E) Pifithrin-α pre-treatment for 1 h prevented Lp(a)-mediated cysteine depletion. (F) Pifithrin-α pre-treatment for 1 h inhibited Lp(a)-induced glutathione reduction. (G) p53 knockdown via siRNA abolished Lp(a)-triggered upregulation of p53 and ACSL4 as well as downregulation of SLC7A11 and GPX4. (H) p53 knockdown via siRNA attenuated Lp(a)-induced cardiomyocyte death. (I) p53 knockdown via siRNA suppressed Lp(a)-enhanced FerroOrange fluorescence intensity. (J) p53 knockdown via siRNA mitigated Lp(a)-elevated intracellular MDA levels. (K) p53 knockdown via siRNA reversed Lp(a)-mediated cysteine depletion. (L) p53 knockdown via siRNA prevented Lp(a)-induced glutathione reduction. *P < 0.01 versus the control group; #P < 0.01 versus the Lp(a) group. The values are expressed as mean ± SD (n = 6 per group).
