title: PKCη deficiency improves lipid metabolism and atherosclerosis in apolipoprotein E-deficient mice.
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.
authors.affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. torisuk@kcu.med.kyushu-u.ac.jp.|Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. torisuk@kcu.med.kyushu-u.ac.jp.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Torisu
authors.affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Xueli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Nonaka
authors.affiliation: Translational Research Department, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 17-10 Nihonbashi, Koami-cho, Chuo-ku, Tokyo, 103-8405, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Kaji
authors.affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.|Research Center for Nucleotide Pool, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tsuchimoto
authors.affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.|Counseling and Health Center, Faculty of Arts and Science, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kajitani
authors.affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.|Research Center for Nucleotide Pool, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Sakumi
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Torisu
authors.affiliation: Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chida
authors.affiliation: Department of Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Katsuo
authors.initials: K
authors.lastname: Sueishi
authors.affiliation: Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hata
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
authors.affiliation: Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kiyohara
authors.affiliation: Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.|Research Center for Nucleotide Pool, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Nakabeppu
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency*; D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D059305:Diet, High-Fat; D004198:Disease Susceptibility; D050171:Dyslipidemias / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism; D018384:Oxidative Stress; D011493:Protein Kinase C / Q000172:deficiency*
chemical_list: D001057:Apolipoproteins E; C081975:protein kinase C eta; D011493:Protein Kinase C