Mechanistic insights into lipoprotein(a)-induced cardiomyocyte ferroptosis via ROS/p38/p53 signaling - Report - MDSpire

Mechanistic insights into lipoprotein(a)-induced cardiomyocyte ferroptosis via ROS/p38/p53 signaling

  • By

  • Yujia Li

  • Xi Chen

  • Chuan He

  • Yukai Zhang

  • Tiechao Jiang

  • July 13, 2026

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Clinical Report: Exploring the Mechanisms of Lipoprotein(a) Induced Ferroptosis

Overview

This study investigates the role of lipoprotein(a) [Lp(a)] in inducing ferroptosis in cardiomyocytes through specific signaling pathways. Activation of p38 MAPK and p53 are identified as critical mediators in this process, contributing to cardiomyocyte injury.

Background

Lipoprotein(a) is recognized as a residual cardiovascular risk factor, particularly in patients with elevated lipid levels. Despite lowering LDL cholesterol, many patients remain at risk for cardiovascular events due to high Lp(a) levels, which have been associated with increased mortality. Understanding the mechanisms by which Lp(a) affects cardiomyocytes is crucial.

Data Highlights

FindingDetails
Ferroptosis InductionLp(a) triggers ferroptosis in AC16 human cardiomyocytes.
p38 MAPK Activationp38 MAPK phosphorylation increases in response to Lp(a).
p53 ActivationNuclear translocation of p53 is driven by p38 activation.
ROS LevelsLp(a) exposure increases intracellular reactive oxygen species.
In Vivo ValidationCardiac dysfunction in Lp(a)-treated C57BL/6J mice confirms findings.

Key Findings

  • Lp(a) induces ferroptosis in cardiomyocytes through a redox-sensitive pathway.
  • Activation of p38 MAPK is central to the ferroptotic process triggered by Lp(a).
  • Pharmacological blockade of p38 significantly reduces ferroptotic markers.
  • p53 activation is necessary for Lp(a)-induced lipid peroxidation and cell death.
  • Increased ROS levels are a key factor in Lp(a)-mediated cardiomyocyte injury.

Clinical Implications

Targeting the p38 MAPK and p53 pathways may provide insights into Lp(a)-induced cardiomyocyte injury.

Conclusion

This study elucidates the mechanisms by which Lp(a) induces ferroptosis in cardiomyocytes, emphasizing the roles of p38 MAPK and p53.

Related Resources & Content

  1. Journal of Gastroenterology, 2025 -- Ferroptosis: Mechanisms and Implications in Hepatic Disorders
  2. Frontiers in Immunology, 2026 -- OxLDL-induced ferroptosis and pyroptosis in atherosclerosis: a mini review
  3. Frontiers in Immunology, 2026 -- Ferroptosis in arterial atherosclerosis: mechanistic hypotheses, cell type specific vulnerabilities, translational biomarkers, and therapeutic opportunities
  4. Frontiers in Cardiovascular Medicine, 2026 -- Iron-dependent ferroptosis in cardiac microvascular endothelial cells: a key link between dysregulated iron homeostasis and microcirculatory injury during myocardial ischemia-reperfusion
  5. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines | Circulation
  6. Novartis Investor Presentation Q1 2026
  7. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines | Circulation
  8. ROS-mediated ferroptosis and pyroptosis in cardiomyocytes: An update - ScienceDirect

Original Source(s)

Mechanistic insights into lipoprotein(a)-induced cardiomyocyte ferroptosis via ROS/p38/p53 signaling

  • by Yujia Li, Xi Chen, Chuan He, Yukai Zhang, Tiechao Jiang

  • July 13, 2026

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