Downregulation of cPLA2 suppress atherosclerotic lesion formation in apolipoprotein-E deficient mice.

• Project/Area Number: 25461374
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kumamoto University
• Principal Investigator: Matsumura Takeshi 熊本大学, 医学部附属病院, 講師 (20398192)
• Co-Investigator(Kenkyū-buntansha): SENOKUCHI Takafumi 熊本大学, 大学院生命科学研究部, 助教 (00530320) ; 本島 寛之 熊本大学, 医学部附属病院, 助教 (40398201)
• Co-Investigator(Renkei-kenkyūsha): MOTOSHIMA Hiroyuki 熊本大学, 医学部附属病院, 助教 (40398201)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 動脈硬化症 / 脂質代謝異常

Outline of Final Research Achievements

We investigated the anti-atherogenic effects on cPLA2 and apoE double knockout mice (cPLA2/apoE KO mice). PPARgannma activity was increased in peritoneal macrophage of cPLA2/apoE KO mice. LPS-induced mRNA expression of TNF-alpha and MCP-1 was decreased, and mRNA expression ABCA1/G1 was increased in peritoneal macrophage of cPLA2/apoE KO mice. Moreover, atherosclerotic lesion formation on cPLA2/apoE KO mice was lower than that on control apoE KO mice. These results suggest that cPLA2 is involved in atherosclerotic lesion formation in apoE KO mice, and that may be therapeutic target for diabetic macrovascular complications.

Research Products

• [Journal Article] Non-invasive measurement of skin autofluorescence to evaluate diabetic complications (2016)
  • Author(s): Yamanaka M, Matsumura T, Ohno R, Fujiwara Y, Shinagawa M, Sugawa H, Hatano K, Shirakawa J, Kinoshita H, Ito K, Sakata N, Araki E, Nagai R
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 58 Issue: 2 Pages: 135-140
  • DOI: 10.3164/jcbn.15-132
  • NAID: 130005132521
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Journal Article] Insulin requirement profiles in Japanese hospitalized subjects with type 2 diabetes treated with basal-bolus insulin therapy (2015)
  • Author(s): Shimoda S, Okubo M, Koga K, Sekigami T, Kawashima J, Kukidome D, Igata M, Ishii N, Shimakawa A, Matsumura T, Motoshima H, Furukawa N, Nishida K, Araki E
  • Journal Title: Endocrine Journal Volume: 62 Issue: 2 Pages: 209-216
  • DOI: 10.1507/endocrj.EJ14-0487
  • NAID: 130004704365
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-gamma activation. (2015)
  • Author(s): Fukuda K, Matsumura T, Senokuchi T, Ishii N, Kinoshita H, Yamada S, Murakami S, Nakao S, Motoshima H, Kondo T, Kukidome D, Kawasaki S, Kawada T, Nishikawa T, Araki E
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 457 Pages: 23-30
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation. (2014)
  • Author(s): Fukuda K, Matsumura T, Senokuchi T, Ishii N, Kinoshita H, Yamada S, Murakami S, Nakao S, Motoshima H, Kondo T, Kukidome D, Kawasaki S, Kawada T, Nishikawa T, Araki E
  • Journal Title: Biochem Biophys Res Commun Volume: 457 Issue: 1 Pages: 23-20
  • DOI: 10.1016/j.bbrc.2014.12.063
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The serine protease prostasin regulates hepatic insulin sensitivity by modulating TLR4 signalling. (2014)
  • Author(s): Uchimura K, Hayata M, Mizumoto T, Miyasato Y, Kakizoe Y, Morinaga J, Onoue T, Yamazoe R, Ueda M, Adachi M, Miyoshi T, Shiraishi N, Ogawa W, Fukuda K, Kondo T, Matsumura T, Araki E, Tomita K, Kitamura K.
  • Journal Title: Nat Commun. Volume: 11 Issue: 1 Pages: 3428-3428
  • DOI: 10.1038/ncomms4428
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of the efficacy of sitagliptin and glimepiride dose-up in Japanese patients with type 2 diabetes poorly controlled by sitagliptin and glimepiride in combination. (2014)
  • Author(s): Shimoda S, Iwashita S, Sekigami T, Furukawa N, Matsuo Y, Ichimori S, Goto R, Maeda T, Watanabe E, Kondo T, Matsumura T, Motoshima H, Nishida K, Araki E
  • Journal Title: J Diabetes Investig Volume: 5 Issue: 3 Pages: 320-326
  • DOI: 10.1111/jdi.12151
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mild electrical stimulation with heat shock reduces visceral adiposity and improves metabolic abnormalities in subjects with metabolic syndrome or type 2 diabetes: Randomized crossover trials. (2014)
  • Author(s): Kondo T, Ono K, Kitano S, Matsuyama R, Goto R, Suico MA, Kawasaki S, Igata M, Kawashima J, Motoshima H, Matsumura T, Kai H, Araki E
  • Journal Title: EBioMedicine Volume: 1 Issue: 1 Pages: 80-89
  • DOI: 10.1016/j.ebiom.2014.11.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The role of heat shock response in insulin resistance and diabetes. (2014)
  • Author(s): Kondo T, Motoshima H, Igata M, Kawashima J, Matsumura T, Kai H, Araki E
  • Journal Title: Diabetes Metab J Volume: 38 Issue: 2 Pages: 100-1006
  • DOI: 10.4093/dmj.2014.38.2.100
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Evaluation of a new device for measurement of hemoglobin A1c for Japanese subjects. (2013)
  • Author(s): Shimoda S, Maeda T, Furukawa N, Ichinose K, Taketa K, Igata M, Senokuchi T, Matsumura T, Araki E
  • Journal Title: Diabetol Int Volume: 4 Issue: 4 Pages: 112-116
  • DOI: 10.1007/s13340-013-0141-z
  • NAID: 10031199817
  • Peer Reviewed
• [Journal Article] Regulation of TNFα converting enzyme activity in visceral adipose tissue of obese mice (2013)
  • Author(s): 川崎修二
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 430 Issue: 4 Pages: 1189-1194
  • DOI: 10.1016/j.bbrc.2012.12.086
  • Peer Reviewed
• [Journal Article] Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages (2013)
  • Author(s): 木下博之
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 431 Issue: 2 Pages: 124-130
  • DOI: 10.1016/j.bbrc.2013.01.014
  • Peer Reviewed
• [Journal Article] Efficacy and safety of sitagliptin as add-on therapy on glycemic control and blood glucose fluctuation in Japanese type 2 diabetes subjects ongoing with multiple daily insulin injections therapy (2013)
  • Author(s): Shimoda S, Iwashita S, Ichimori S, Matsuo Y, Goto R, Maeda T, Matsuo T, Sekigami T, Kawashima J, Kondo T, Matsumura T, Motoshima H, Furukawa N, Nishida K, Araki E.
  • Journal Title: Endocrine Journal Volume: 60 Issue: 10 Pages: 1207-1214
  • DOI: 10.1507/endocrj.EJ13-0198
  • NAID: 130004770390
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Association between circulating leukocyte subtype counts and carotid intima-media thickness in Japanese subjects with type 2 diabetes. (2013)
  • Author(s): Matsumura T, Taketa K, Motoshima H, Senokuchi T, Ishii N, Kinoshita H, Fukuda K, Yamada S, Kukidome D, Kondo T, Hisada A, Katoh T, Shimoda S, Nishikawa T, Araki E.
  • Journal Title: Cardiovascular Diabetology Volume: 12(1) Issue: 1 Pages: 177-177
  • DOI: 10.1186/1475-2840-12-177
  • Peer Reviewed
• [Journal Article] Effects of combination therapy with vildagliptin and valsartan in a mouse model of type 2 diabetes. (2013)
  • Author(s): Miyagawa K, Kondo T, Goto R, Matsuyama R, Ono K, Kitano S, Kawasaki S, Igata M, Kawashima J, Matsumura T, Motoshima H, Araki E.
  • Journal Title: Cardiovascular Diabetology Volume: 12(1) Issue: 1 Pages: 160-160
  • DOI: 10.1186/1475-2840-12-160
  • Peer Reviewed
• [Presentation] 非侵襲指先部経皮蛍光AGEs測定による糖尿病細小血管合併症スクリーニング法の臨床的意義 (2015)
  • Author(s): 松村剛, 木下博之, 山中幹宏, 福田一起, 石井規夫, 瀬ノ口隆文, 西川武志, 大野礼一, 永井竜児, 荒木栄一
  • Organizer: 第53回日本糖尿病学会九州地方会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-27
  • Int'l Joint Research
• [Presentation] Non-invasive measurement of skin AGEs and its association with diabetic microvascular complications. (2015)
  • Author(s): Murakami S, Matsumura T, Yamanaka M, Ohno R, Kinoshita H, Senokuchi T, Ishii N, Fukuda K, Nagai R, Araki E
  • Organizer: The 7th AASD Scientific Meeting
  • Place of Presentation: Hong Kong Convention and Exhibition Centre, Hong Kong, China
  • Year and Date: 2015-11-21
  • Int'l Joint Research
• [Presentation] Non-invasive measurement of skin AGEs and its association with diabetic microvascular complications. (2015)
  • Author(s): Matsumura T, Yamanaka M, Ohno R, Kinoshita H, Senokuchi T, Ishii N, Fukuda K, Murakami S, Nagai R, Araki E
  • Organizer: Keystone Symposia Conference-Diabetes: New Insights into Molecular Mechanisms and Therapeutic Strategies
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2015-10-25
  • Int'l Joint Research
• [Presentation] 2型糖尿病における経口糖尿病薬による体重、脂質代謝への影響 (2015)
  • Author(s): 松村剛, 片平聖子, 関谷春花, 藤本有紀, 深田和子, 吉富咲子, 荒木栄一
  • Organizer: 第36回日本肥満学会年次学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-02
  • Int'l Joint Research
• [Presentation] Cellular hypoxia and mitochondrial reactive oxygen species may promote hyperglycaemic damage in a coordinated manner. (2015)
  • Author(s): Sata K, Nishikawa T, Kukidome D, Kajiwara N, Motoshima H, Matsumura T, Araki E
  • Organizer: 51th EASD Annual Meeting
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2015-09-14
  • Int'l Joint Research
• [Presentation] 肥満・メタボリックシンドロームにおける血清脂質値へのコレステロール合成・吸収能の影響 (2015)
  • Author(s): 松村剛, 瀬ノ口隆文, 石井規夫, 木下博之, 福田一起, 山田沙梨恵, 村上彩子, 西川武志, 荒木栄一
  • Organizer: 第47回日本動脈硬化学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2015-07-09
  • Int'l Joint Research
• [Presentation] 肥満2型糖尿病におけるHDL亜分画とインスリン抵抗性との関連性の検討 (2015)
  • Author(s): 松村剛, 瀬ノ口隆文, 石井規夫, 木下博之, 福田一起, 山田沙梨恵, 村上彩子, 本島寛之, 近藤龍也, 西川武志, 荒木栄一
  • Organizer: 第65回日本体質医学会
  • Place of Presentation: 札幌
  • Year and Date: 2015-07-04
  • Int'l Joint Research
• [Presentation] Impacts of Heat Shock Protein 72 in Hepatic Glucose Metabolism in Model Mice of Type 2 Diabetes. (2015)
  • Author(s): Kondo T, Matsuyama R, Kitano S, Goto R, Ono K, Kawashima J, Motoshima H, Matsumura T, Kai H, Araki E
  • Organizer: The 75th ADA scientific meeting
  • Place of Presentation: World Trade Center, Boston, MA, USA
  • Year and Date: 2015-06-05
  • Int'l Joint Research
• [Presentation] Aldosterone excess state causes a chronic inflammation in the pancreatic islet. (2015)
  • Author(s): Goto R, Kondo T, Kitano S, Ono K, Matsuyama R, Igata M, Kawashima J, Matsumura T, Motoshima H, Shimoda S, Araki E
  • Organizer: The 75th ADA scientific meeting
  • Place of Presentation: World Trade Center, Boston, MA, USA
  • Year and Date: 2015-06-05
  • Int'l Joint Research
• [Presentation] 2型糖尿病におけるHDL亜分画とインスリン抵抗性との関連 (2015)
  • Author(s): 松村剛, 木下博之, 本島寛之, 近藤龍也, 瀬ノ口隆文, 石井規夫, 松嶋和美, 杉内博幸, 西川武志, 荒木栄一
  • Organizer: 第112回日本内科学会
  • Place of Presentation: 京都
  • Year and Date: 2015-04-10
  • Int'l Joint Research
• [Presentation] Association between circulating leukocyte subtype counts and carotid intima-media thickness in Japanese subjects with type 2 diabetes. (2014)
  • Author(s): Matsumura T, Senokuchi T, Fukuda K, Ishii N, Kinoshita H, Yamada S, Murakami S, Kondo T, Motoshima H, Nishikawa T, Araki E
  • Organizer: The 6th AASD Scientific Meeting
  • Place of Presentation: SUNTEC, Singapore
  • Year and Date: 2014-12-21 – 2014-12-24
• [Presentation] Statin-mediated PPARγ activation in adipocytes may improve glucose tolerance in high fat-fed mice. (2014)
  • Author(s): Senokuchi T, Matsumura T, Fukuda K, Ishii N, Kinoshita H, Yamada S, Murakami S, Kondo T, Motoshima H, Nishikawa T, Araki E
  • Organizer: The 6th AASD Scientific Meeting
  • Place of Presentation: SUNTEC, Singapore
  • Year and Date: 2014-12-21 – 2014-12-24
• [Presentation] インスリン抵抗性、動脈硬化の発症・進展における組織浸潤マクロファージ増殖の生理学的意義の検討 (2014)
  • Author(s): 瀬ノ口隆文, 山田沙梨恵, 松村剛, 本島寛之, 西川武志, 荒木栄一
  • Organizer: 第26回分子糖尿病学シンポジウム
  • Place of Presentation: 高知
  • Year and Date: 2014-12-06
• [Presentation] 糖尿病と大血管合併症～その発症をいかに防ぐか～ (2014)
  • Author(s): 松村剛
  • Organizer: 第52回日本糖尿病学会九州地方会 教育講演
  • Place of Presentation: 熊本
  • Year and Date: 2014-10-31 – 2014-11-01
  • Invited
• [Presentation] 肥満2型糖尿病におけるHDL亜分画とインスリン抵抗性との関連 (2014)
  • Author(s): 松村剛, 木下博之, 本島寛之, 近藤龍也, 瀬ノ口隆文, 石井規夫, 福田一起, 山田沙梨恵, 村上彩子, 松嶋和美, 杉内博幸, 西川武志, 荒木栄一
  • Organizer: 第35回日本肥満学会
  • Place of Presentation: 宮崎
  • Year and Date: 2014-10-24 – 2014-10-25
• [Presentation] Inhibition of local macrophage growth ameliorates focal inflammation in the plaque and suppresses atherosclerosis in ApoE-deficient mice. (2014)
  • Author(s): Senokuchi T, Yamada S, Negita E, Matsumura T, Nishikawa T, Araki E
  • Organizer: The 9th Metabolic Syndrome, Type 2 Diabetes and Atherosclerosis Congress
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2014-09-12 – 2014-09-13
• [Presentation] Statins improve glucose tolerance in high fat-fed mice possible through PPARγ activation in adipocytes. (2014)
  • Author(s): Fukuda K, Matsumura T, Ishii N, Kinoshita H, Yamada S, Murakami S, Senokuchi T, Kondo T, Motoshima H, Nishikawa T, Araki E
  • Organizer: The 9th Metabolic Syndrome, Type 2 Diabetes and Atherosclerosis Congress
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2014-09-12 – 2014-09-13
• [Presentation] 糖尿病における動脈硬化症進展の体質医学的研究：組織浸潤マクロファージ増殖の意義の検討 (2014)
  • Author(s): 瀬ノ口隆文
  • Organizer: 第64回日本体質医学会 研究奨励賞受賞講演
  • Place of Presentation: 大阪
  • Year and Date: 2014-09-06 – 2014-09-07
• [Presentation] Therepeutic pproach focused on the inactivation of macrophages for diabetic macroangiopathy. (2013)
  • Author(s): 松村剛
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] 肥満・メタボリックシンドロームにおける血清脂質値へのコレステロール合成・吸収能の影響 (2013)
  • Author(s): 松村剛
  • Organizer: 第28回日本糖尿病合併症学会
  • Place of Presentation: 旭川
• [Presentation] 肥満・メタボリックシンドロームにおける血清脂質値へのコレステロール合成・吸収能の影響 (2013)
  • Author(s): 松村剛
  • Organizer: 第63回日本体質医学会
  • Place of Presentation: 久留米
• [Presentation] 肥満・メタボリックシンドロームにおける血清脂質値へのコレステロール合成・吸収能の影響 (2013)
  • Author(s): 松村剛
  • Organizer: 第51回日本糖尿病学会九州地方会
  • Place of Presentation: 沖縄