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HMGB-1 Mediates The Exacerbation of Anaphylactic Shock Under Hyperlipidemic Conditions

Zikang Liu1, Tingting Ding1, Jing Wan1

  • 1Department of Forensic Medicine, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, China.

Journal of Cellular Physiology
|February 25, 2026
PubMed

Insights

Coronary heart disease worsens anaphylaxis by increasing endothelial damage and HMGB-1 release. Targeting HMGB-1 may alleviate severe anaphylactic shock.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Pathophysiology

Background:

  • Coronary heart disease (CHD) is known to exacerbate anaphylactic shock.
  • The precise mechanisms underlying this interaction remain unclear.

Purpose of the Study:

  • To elucidate the mechanisms by which coronary heart disease exacerbates anaphylaxis.
  • To investigate the role of oxidized low-density lipoprotein (ox-LDL) and High-Mobility Group Box-1 (HMGB-1) in this process.

Main Methods:

  • Atherosclerosis was induced in LDLR-/- mice using a high-fat diet.
  • Anaphylaxis was triggered by ovalbumin (OVA) challenge.
  • In vitro studies utilized human umbilical vein endothelial cells (HUVECs) and mast cells exposed to ox-LDL.

Main Results:

  • LDLR-/- mice exhibited exacerbated anaphylaxis with increased mortality, hypothermia, and pulmonary edema compared to wild-type mice.
  • Oxidized low-density lipoprotein (ox-LDL) exposure increased High-Mobility Group Box-1 (HMGB-1) release from endothelial cells and induced histamine release from mast cells.
  • HMGB-1 levels were elevated, and PECAM-1 expression was reduced in the lungs of mice with atherosclerosis during anaphylaxis.
  • Inhibition of H1 receptors or HMGB-1 significantly improved survival and attenuated hypothermia.

Conclusions:

  • Oxidized low-density lipoprotein (ox-LDL) exacerbates endothelial cell damage, leading to increased High-Mobility Group Box-1 (HMGB-1) release and vascular permeability.
  • These changes contribute to the worsening of anaphylaxis into anaphylactic shock.
  • High-Mobility Group Box-1 (HMGB-1) represents a potential therapeutic target for mitigating anaphylactic shock in patients with coronary heart disease.

Keywords:
HMGB‐1Ox‐LDLanaphylaxishyperlipidemiavascular permeability

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