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. We found that the dyslipidemia observed in Prkch+/+Apoe−/− mice was improved in Prkch−/−Apoe−/− mice. HFD‐induced liver steatosis was markedly attenuated in Prkch−/−Apoe−/− mice. Consistent with improvements of dyslipidemia, atherosclerotic lesions were decreased in HFD‐fed Prkch−/−Apoe−/− mice.