Manipulation of Leucocytic NADPH Oxidase Maturation May Drive Macrophage Differentiation and Affect Atherogenesis

Abstract Atherosclerosis is a process of arterial intima thickening caused by lipid deposition as consequence insufficient efferocytosis apoptotic cells M2 macrophages and excessive inflammatory cytokine secretion from M1 macrophages. NADPH oxidase 2 (NOX2) recognized major source ROS for enhancing macrophage functional polarization. We previously found that human contain significant amount endoplasmic reticulum (ER)-retained gp91 phox, component NOX2, which may hinder the formation NOX2. To address role NOX2 in atherosclerosis, we established mouse model bearing Apoe −/−and CYBBpoint mutation (C1024T), leads to ER-retained phoxin immune cells. also developed method targeted delivery SERCA inhibitor with poly (lacticcoglycolic acid) (PLGA) nanoparticles (NPs), promote glycosylation maturation phox. first oxLDL-administrated expressed increased marker CD163 efferocytotic ability after being treated NPs. there was an those mice (C1024T) treatment Macrophage ATP-binding cassette transporters, could decrease cholesterol overloading macrophages, were upregulated Our results demonstrated NPs not only can recover but facilitate differentiation M2-like enhanced activity efflux.