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. 2026 Jul 13;13:1858249. doi: 10.3389/fmed.2026.1858249

FIGURE 4.

Panel figure of western blots and bar charts showing protein expression and quantitative measures in AC16 cells under different conditions, including controls, Pifithrin, Lp(a), and P53 interventions. Western blots display bands for P53, SLC7A11, GPX4, ACSL4, and β-Actin across conditions. Bar graphs present cell death ratios, fluorescent intensity, and relative levels of MDA, cysteine, and GSH, with statistically significant differences marked by asterisks and p-values. Data illustrate effects of Lp(a) and P53 signaling or silencing on oxidative stress and cell viability.

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).