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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Circulating 4-Hydroxynonenal Is Associated with Clinical Severity in ST-Segment Elevation Myocardial Infarction

  • Ángel Priego-Ranero1,2,3
  • Brandon Fisher-Bautista1
  • Rashidi Springall1
  • Luis M. Amezcua-Guerra1
  • Héctor González-Pacheco4
  • Pedro Ruiz-Garcia1
  • Betsabé Jaramillo-Antonio5
  • Malinalli Brianza-Padilla1
  • Gabriela Fonseca-Camarillo1
5 affiliations
  1. 1Departamento de Inmunología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico
  2. 2Departamento de Hemodinámica, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico
  3. 3Programa de Maestría en Ciencias Médicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
  4. 4Unidad de Cuidados Coronarios, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico
  5. 5Laboratorio de Medicina Traslacional, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico
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Abstract

Oxidative stress and ferroptosis are increasingly recognized as key contributors to the pathogenesis of ST-segment elevation myocardial infarction (STEMI), although the clinical relevance of circulating molecules linked to these processes remains insufficiently defined. The present study evaluated serum levels of the lipid peroxidation marker 4-hydroxynonenal (4-HNE), as well as glutathione peroxidase 4 (GPX4), in patients with STEMI and controls, and explored their relationship with clinical severity. Serum concentrations of 4-HNE and GPX4 were measured, and their associations with clinical risk scores and major outcomes were analyzed using correlation and regression methods. Compared with controls, patients with STEMI showed significantly higher 4-HNE concentrations (median, 1220.2 [IQR, 806–1453] vs. 38.7 [15.6–584]; p < 0.001), whereas GPX4 levels were significantly lower in STEMI patients (median, 8.85 [8–10.56] vs. controls 10.50 [9.31–12.11]; p = 0.003). Increased 4-HNE levels were positively associated with the TIMI score (ρ = 0.385, FDR-adjusted p = 0.026) and Killip–Kimball class (ρ = 0.329, p = 0.016; FDR-adjusted p = 0.041), suggesting a relationship with greater clinical severity. Although unadjusted analysis indicated an association between higher 4-HNE concentrations and cardiovascular mortality (OR, 1.0033; 95% CI, 1.0004–1.0083; p = 0.0176), this finding was not significant after multivariable adjustment. Overall, these findings indicate that STEMI is associated with increased lipid peroxidation and reduced GPX4 levels, supporting the involvement of ferroptosis-related pathways in acute myocardial infarction. Elevated 4-HNE levels were also associated with greater clinical severity.

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Cite

BibTeXRIS
BibTeX
@article{priegoranero2026circulating,
  title = {{Circulating 4-Hydroxynonenal Is Associated with Clinical Severity in ST-Segment Elevation Myocardial Infarction}},
  author = {Ángel Priego-Ranero and Brandon Fisher-Bautista and Rashidi Springall and Luis M. Amezcua-Guerra and Héctor González-Pacheco and Pedro Ruiz-Garcia and Betsabé Jaramillo-Antonio and Malinalli Brianza-Padilla and Gabriela Fonseca-Camarillo},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27219694},
  url = {https://www.mdpi.com/1422-0067/27/21/9694},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Circulating 4-Hydroxynonenal Is Associated with Clinical Severity in ST-Segment Elevation Myocardial Infarction
AU  - Ángel Priego-Ranero
AU  - Brandon Fisher-Bautista
AU  - Rashidi Springall
AU  - Luis M. Amezcua-Guerra
AU  - Héctor González-Pacheco
AU  - Pedro Ruiz-Garcia
AU  - Betsabé Jaramillo-Antonio
AU  - Malinalli Brianza-Padilla
AU  - Gabriela Fonseca-Camarillo
PY  - 2026
DA  - 2026/10/29
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219694
UR  - https://www.mdpi.com/1422-0067/27/21/9694
AB  - Oxidative stress and ferroptosis are increasingly recognized as key contributors to the pathogenesis of ST-segment elevation myocardial infarction (STEMI), although the clinical relevance of circulating molecules linked to these processes remains insufficiently defined. The present study evaluated serum levels of the lipid peroxidation marker 4-hydroxynonenal (4-HNE), as well as glutathione peroxidase 4 (GPX4), in patients with STEMI and controls, and explored their relationship with clinical severity. Serum concentrations of 4-HNE and GPX4 were measured, and their associations with clinical risk scores and major outcomes were analyzed using correlation and regression methods. Compared with controls, patients with STEMI showed significantly higher 4-HNE concentrations (median, 1220.2 [IQR, 806–1453] vs. 38.7 [15.6–584]; p < 0.001), whereas GPX4 levels were significantly lower in STEMI patients (median, 8.85 [8–10.56] vs. controls 10.50 [9.31–12.11]; p = 0.003). Increased 4-HNE levels were positively associated with the TIMI score (ρ = 0.385, FDR-adjusted p = 0.026) and Killip–Kimball class (ρ = 0.329, p = 0.016; FDR-adjusted p = 0.041), suggesting a relationship with greater clinical severity. Although unadjusted analysis indicated an association between higher 4-HNE concentrations and cardiovascular mortality (OR, 1.0033; 95% CI, 1.0004–1.0083; p = 0.0176), this finding was not significant after multivariable adjustment. Overall, these findings indicate that STEMI is associated with increased lipid peroxidation and reduced GPX4 levels, supporting the involvement of ferroptosis-related pathways in acute myocardial infarction. Elevated 4-HNE levels were also associated with greater clinical severity.
SN  - 1422-0067
ER  -