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Review
. 2025 Feb;33(2):767-784.
doi: 10.1007/s10787-024-01586-w. Epub 2024 Nov 2.

Targeting high-mobility-group-box-1-mediated inflammation: a promising therapeutic approach for myocardial infarction

Shrutika Date  1 , Lokesh Kumar Bhatt  2
Affiliations
Review

Targeting high-mobility-group-box-1-mediated inflammation: a promising therapeutic approach for myocardial infarction

Shrutika Date et al. Inflammopharmacology. 2025 Feb.

Abstract

Myocardial ischemia, resulting from coronary artery blockage, precipitates cardiac arrhythmias, myocardial structural changes, and heart failure. The pathophysiology of MI is mainly based on inflammation and cell death, which are essential in aggravating myocardial ischemia and reperfusion injury. Emerging research highlights the functionality of high mobility group box-1, a non-histone nucleoprotein functioning as a chromosomal stabilizer and inflammatory mediator. HMGB1's release into the extracellular compartment during ischemia acts as damage-associated molecular pattern, triggering immune reaction by pattern recognition receptors and exacerbating tissue inflammation. Its involvement in signaling pathways like PI3K/Akt, TLR4/NF-κB, and RAGE/HMGB1 underscores its significance in promoting angiogenesis, apoptosis, and reducing inflammation, which is crucial for MI treatment strategies. This review highlights the complex function of HMGB1 in the pathogenesis of myocardial infarction by summarizing novel findings on the protein in ischemic situations. Understanding the mechanisms underlying HMGB1 could widen the way to specific treatments that minimize the severity of MI and enhance patient outcomes.

Keywords: High mobility group box-1; Inflammation; Myocardial ischemia; TLR4.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that there are no competing interests. Ethical approval and consent to participate: Not applicable. Consent for publication: Not applicable.

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