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

Abstract

Coronary heart disease (CHD) may worsen anaphylactic shock, but the exact mechanism is unknown. This study aimed to investigate the mechanisms by which coronary heart disease exacerbates anaphylaxis.C57BL/6 (WT) mice and LDLRmice were fed a high-fat diet for 20 weeks to develop atherosclerosis. Anaphylaxis was then induced using ovalbumin (OVA). Compared to WT mice, LDLRmice showed lower body temperature, worse pulmonary edema and higher mortality. Pulmonary endothelial cell CD31 (PECAM-1) expression decreased, but serum HMGB-1 levels increased. In vitro experiments found that ox-LDL exposure led to more HMGB-1 release from HUVECs. Moreover, ox-LDL induced mast cells release of histamine, upregulating the expression of more H1 receptors (H1R) in HUVECs, thereby further promoting HMGB-1 release. Pretreatment with an H1R inhibitor (chlorpheniramine) or an HMGB-1 neutralizing antibody improved survival and attenuated hypothermia in mice. In summary, ox-LDL exacerbates endothelial cell damage, resulting in increased HMGB-1 release and vascular permeability, which may worsen anaphylaxis to anaphylactic shock. The mechanisms are not fully understood, but HMGB-1 could be a potential target for future alleviation of anaphylactic shock.