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

Kumiko Torisu, Xueli Zhang, Mari Nonaka, Takahide Kaji, Daisuke Tsuchimoto, Kosuke Kajitani, Kunihiko Sakumi, Takehiro Torisu, Kazuhiro Chida, Katsuo Sueishi, Michiaki Kubo, Jun Hata, Takanari Kitazono, Yutaka Kiyohara, Yusaku Nakabeppu

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5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1030-1048
Number of pages19
JournalGenes to Cells
Volume21
Issue number10
DOIs
Publication statusPublished - 01-10-2016

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

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    Torisu, K., Zhang, X., Nonaka, M., Kaji, T., Tsuchimoto, D., Kajitani, K., Sakumi, K., Torisu, T., Chida, K., Sueishi, K., Kubo, M., Hata, J., Kitazono, T., Kiyohara, Y., & Nakabeppu, Y. (2016). PKCη deficiency improves lipid metabolism and atherosclerosis in apolipoprotein E-deficient mice. Genes to Cells, 21(10), 1030-1048. https://doi.org/10.1111/gtc.12402