HIF-1A, NF-ΚB, AND NRF2 IN ACUTE MYOCARDIAL INFARCTION WITH ST-SEGMENT ELEVATION: A SYSTEMATIC REVIEW

Abstract

Introduction: ST-segment elevation myocardial infarction (STEMI) remains associated with high morbidity and mortality, with its inflammatory, adaptive, and antioxidant responses signaled by transcription factors such as NF-κB, HIF-1α, and Nrf2. Understanding the expression of these transcription factors in infarcted patients is essential to integrate the mechanisms involved and associate them with patient prognosis. Method: This systematic review was registered in PROSPERO (code: 1079538) and conducted according to the PRISMA 2020 guidelines. Searches were performed in the PubMed, Embase, and LILACS/BVS databases using the terms: “myocardial infarction”, “risk prediction”, “risk stratification”, “biomarker”, “outcome”, “prognostic”, “Nrf2”, “NFKB”, and “HIF”. Randomized clinical trials, case-control studies, and cohort studies in adult humans that evaluated inflammatory, hypoxic, or antioxidant biomarkers were included. The risk of bias was assessed using the Jadad scale. Results: Of the 924 articles initially found, four met the inclusion criteria. NF-κB proved relevant in inflammatory activation and in the modulation of pro- and anti-inflammatory cytokines. HIF-1α was associated with the extent of the infarcted area, cellular adaptation to hypoxia, and angiogenesis. No study directly evaluated Nrf2, although biomarkers related to it were cited (GPX4, FSP1, and FTH1), highlighting its importance in antioxidant action and the regulation of ferroptosis. Conclusion: The study highlighted the relevance of NF-κB and HIF-1α in the inflammatory and adaptive response in STEMI, while the lack of direct investigation on Nrf2 points to a critical gap in the knowledge of antioxidant mechanisms. New research involving Nrf2 may complement the molecular understanding of post-MI damage and repair, providing support for the development of personalized therapeutic strategies.