Paraoxonase 1‐treated oxLDL promotes cholesterol efflux from macrophages by stimulating the PPARγ–LXRα–ABCA1 pathway

Abstract

Here, we investigate the mechanism through which paraoxonase 1 ( PON 1) may regulate cholesterol efflux. Pretreatment of ox LDL with PON 1 (ox LDL – PON 1) contributed to the formation of Lyso PC . In J774 macrophages, ox LDL – PON 1 increased cholesterol efflux by more than 47% compared to ox LDL alone. ox LDL – PON 1 significantly increased mRNA and protein expression of ABCA 1 and ABCG 1, as well as of PPAR γ and LXR α compared to ox LDL alone. Intraperitoneal injection of ox LDL – PON 1‐ or Lyso PC ‐treated J774 macrophages significantly increased the fecal elimination of macrophage‐derived cholesterol in these mice. Our results suggest that PON 1 stimulates cholesterol efflux via a mechanism that involves oxidized phospholipid hydrolysis.