» Articles » PMID: 39487941

Targeting High-mobility-group-box-1-mediated Inflammation: a Promising Therapeutic Approach for Myocardial Infarction

Overview
Specialty Pharmacology
Date 2024 Nov 2
PMID 39487941
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Molecular Mechanisms Underlying Heart Failure and Their Therapeutic Potential.

Fonseka O, Gare S, Chen X, Zhang J, Alatawi N, Ross C Cells. 2025; 14(5).

PMID: 40072053 PMC: 11899429. DOI: 10.3390/cells14050324.

References
1.
Andersson U, Tracey K . HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol. 2011; 29:139-62. PMC: 4536551. DOI: 10.1146/annurev-immunol-030409-101323. View

2.
Andersson U, Antoine D, Tracey K . The functions of HMGB1 depend on molecular localization and post-translational modifications. J Intern Med. 2014; 276(5):420-4. DOI: 10.1111/joim.12309. View

3.
Andersson U, Tracey K, Yang H . Post-Translational Modification of HMGB1 Disulfide Bonds in Stimulating and Inhibiting Inflammation. Cells. 2021; 10(12). PMC: 8699546. DOI: 10.3390/cells10123323. View

4.
Banerjee S, de Freitas A, Friggeri A, Zmijewski J, Liu G, Abraham E . Intracellular HMGB1 negatively regulates efferocytosis. J Immunol. 2011; 187(9):4686-94. PMC: 3197890. DOI: 10.4049/jimmunol.1101500. View

5.
Belgrano F, de Abreu da Silva I, Bastos de Oliveira F, Fantappie M, Mohana-Borges R . Role of the acidic tail of high mobility group protein B1 (HMGB1) in protein stability and DNA bending. PLoS One. 2013; 8(11):e79572. PMC: 3821859. DOI: 10.1371/journal.pone.0079572. View