PKCη deficiency improves lipid metabolism and atherosclerosis in apolipoprotein E-deficient mice

Genomewide association studies have shown that a nonsynonymous single nucleotide polymorphism in PRKCH is associated with cerebral infarction and atherosclerosis-related complications. We examined the role of PKCη in lipid metabolism and atherosclerosis using apolipoprotein E-deficient (Apoe^−/−) mice. PKCη expression was augmented in the aortas of mice with atherosclerosis and exclusively detected in MOMA2-positive macrophages within atherosclerotic lesions. Prkch^+/+Apoe^−/− and Prkch^−/−Apoe^−/− mice were fed a high-fat diet (HFD), and the dyslipidemia observed in Prkch^+/+Apoe^−/− mice was improved in Prkch^−/−Apoe^−/− mice, with a particular reduction in serum LDL cholesterol and phospholipids. Liver steatosis, which developed in Prkch^+/+Apoe^−/− mice, was improved in Prkch^−/−Apoe^−/− mice, but glucose tolerance, adipose tissue and body weight, and blood pressure were unchanged. Consistent with improvements in LDL cholesterol, atherosclerotic lesions were decreased in HFD-fed Prkch^−/−Apoe^−/− mice. Immunoreactivity against 3-nitrotyrosine in atherosclerotic lesions was dramatically decreased in Prkch^−/−Apoe^−/− mice, accompanied by decreased necrosis and apoptosis in the lesions. ARG2 mRNA and protein levels were significantly increased in Prkch^−/−Apoe^−/− macrophages. These data show that PKCη deficiency improves dyslipidemia and reduces susceptibility to atherosclerosis in Apoe^−/− mice, showing that PKCη plays a role in atherosclerosis development.