Soluble rCD93 containing D1 inhibited HMGB1-induced proinflammatory cytokine production and intracellular mitogen-activated protein kinase (MAPK)/nuclear factor (NF)-κB activation in macrophages and VSMCs, thereby attenuating CaCl<sub>2</sub>-induced and angiotensin II-infused AAA models. Here, HMGB1 is linked to triple-A syndrome.