高脂血症条件下における高遷移金属ボックス1（HMGB-1）を介したアナフィラキシーショックの増悪

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 LDLR^-/- mice were fed a high-fat diet for 20 weeks to develop atherosclerosis. Anaphylaxis was then induced using ovalbumin (OVA). Compared to WT mice, LDLR^-/- mice 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.