Role of GPNMB in Foam Cells Formation and Atherosclerosis Progression

Currently, both reliable biomarkers for disease monitoring and specific therapeutic targets are needed to combat atherosclerosis, one of the dangerous lipid metabolism disorders. We observed attenuation of atherosclerosis in a GPNMB auto-mutant (GpnmbR150X) mouse model as well as in a myeloid-specific Gpnmb-knockout mouse model. Furthermore, in GpnmbR150X BMDMs, we observed that impaired lipid droplet formation, enhanced lipid oxidative metabolism, and more robust lipid degradation by the lysosomal pathway suppressed the macrophage foaming, thereby reducing the atherosclerotic burden of excess OxLDL. To investigate how GPNMB affected the macrophage foaming, we performed bulk RNA-seq analysis of BMDMs from GpnmbR150X mouse or control mouse and OxLDL-treated BMDMs from GpnmbR150X mouse or control mouse.