Identification of Myeloid Protein Kinase C Epsilon as a Novel Atheroprotective Gene

PRKCE expression is decreased in vulnerable human plaques and PKCɛ decreases in mouse macrophages upon lipid loading. mɛKO plaques are larger and exhibit markers of vulnerability. With no differences in SR (scavenger receptor) expression, the impact of PKCɛ deletion is more subtle than simple SR dysregulation. RNA sequencing implicates higher expression of genes involved in endocytosis, and mɛKO macrophages have significantly more lipid-containing endosomes. The data define the atherophenotype of mɛKO mice and demonstrate that PKCɛ restricts lipid uptake into macrophages by a mechanism independent of SR expression. Taken together, these studies identify PKCɛ as a novel atheroprotective gene, laying the foundation for mechanistic studies on the endocytic signaling networks responsible for the phenotype.