HMGB1 binds to modified LDL and enhances its uptake by macrophages

Abstract

Atherosclerosis is an inflammatory cardiovascular disease which is commonly described as lipid accumulation in the intimal region of the arterial wall that eventually causes myocardial infarction and stroke. The high mobility group box 1 (HMGB1) is a nuclear protein which plays important role in immunity and inflammation. HMGB1 is elevated in atherosclerotic lesions which indicated its possible involvement in the progression of atherosclerosis. In this study, we observed that HMGB1 directly binds to LDL and modified LDL, but not to HDL. Moreover, modified LDL uptake by THP-1 macrophages was increased time- and dose-dependent manner in the presence of HMGB1. Addition of soluble CD36 scavenger receptor protein reversed the HMGB1 effect on modified LDL uptake. Further, HMGB1 bound to CD36 and CD36 overexpression enhanced the HMGB1 effect on modified LDL uptake. Collectively, our data indicates that HMGB1 bound to modified LDL and increased their uptake by macrophage through CD36 scavenger receptor.