Development of therapeutic drug for steatohepatitis by liver-specific bio-nanocapsules equipped with RNAi targeting TTC39B

• Project/Area Number: 18H03532
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Osaka University
• Principal Investigator: Koseki Masahiro 大阪大学, 医学系研究科, 助教 (10467582)
• Co-Investigator(Kenkyū-buntansha): 黒田 俊一 大阪大学, 産業科学研究所, 教授 (60263406)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
• Keywords: 脂肪肝炎 / バイオナノカプセル / TTC39B / PCSK9 / コレステロール / 核酸医薬 / 肝特異的 / 肥満マウス / ７ケトコレステロール

Outline of Final Research Achievements

We developed a new steatohepatitis model by focusing on, a dietary oxidized cholesterol, 7-ketocholesterol (7KC). Administration of 7KC resulted in decrease in mitochondrial activity, modulation of autophagy mechanism, expression of inflammatory cytokines in obesity/diabetes model mice. Then, we reported that 7KC exacerbated lipid accumulation, inflammatory cell infiltration, and liver fibrosis (Frontier in Endocrinology 2020). In addition, we also succeeded in creating a “steatohepatitis-related cardiomyopathy” in a rodent NSH model (in submission). This is the first model showing NLRP3 inflammasome activation and cardiac dysfunction due to cholesterol accumulation in both the liver and heart.

Academic Significance and Societal Importance of the Research Achievements

本研究で開発したモデルはこれまでの脂肪肝炎モデルに比し、肝線維化の進行が早く、これまでのメチオニン・コリン欠乏食（MCD）による脂肪肝炎と比較して、よりヒトの脂肪肝炎の組織像に近い所見がえられており、今後の核酸医薬の試験に有用であると考えられる。
RNAi搭載バイオナノカプセルは、均質な粒子径を売るための条件検討がほぼ完了した。
より迅速な、核酸医薬搭載バイオナノカプセルの効果判定試験が可能となった。

Research Products

• [Journal Article] A Resuscitated Case of Acute Myocardial Infarction with both Familial Hypercholesterolemia Phenotype Caused by Possibly Oligogenic Variants of the <i>PCSK9</i> and <i>ABCG5</i> Genes and Type I CD36 Deficiency (2022)
  • Author(s): Nishikawa Ryo、Furuhashi Masato、Hori Mika、Ogura Masatsune、Harada-Shiba Mariko、Okada Takeshi、Koseki Masahiro、Kujiraoka Takeshi、Hattori Hiroaki、Ito Ryosuke、Muranaka Atsuko、Kokubu Nobuaki、Miura Tetsuji
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 29 Issue: 4 Pages: 551-557
  • DOI: 10.5551/jat.58909
  • NAID: 130007992205
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2022-04-01
  • Peer Reviewed / Open Access
• [Journal Article] Development and Clinical Application of an Enzyme-Linked Immunosorbent Assay for Oxidized High-Density Lipoprotein (2021)
  • Author(s): Okada Takeshi、Sumida Mizuki、Ohama Tohru、Katayama Yuki、Saga Ayami、Inui Hiroyasu、Kanno Kotaro、Masuda Daisaku、Koseki Masahiro、Nishida Makoto、Sakata Yasushi、Yamashita Shizuya
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 28 Issue: 7 Pages: 703-715
  • DOI: 10.5551/jat.56887
  • NAID: 130008060163
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2021-07-01
  • Peer Reviewed / Open Access
• [Journal Article] Dietary oxysterol, 7-Ketocholesterol accelerates hepatic lipid accumulation and macrophage infiltration in obese Mice (2021)
  • Author(s): J. Chang, M. oseki, A. Saga, K. Kanno, T. Higo, D. Okuzaki, T. Okada, H. Inui, K. Tanaka, M. Asaji, Y. Zhu, K. Yamada, M. Ono, T. Saibara, I Ichi, T. Ohama, M. Nishida, S. Yamashita, Y. Sakata
  • Journal Title: Front Endocrinol (Lausanne) Volume: 11 Pages: 614692-614692
  • DOI: 10.3389/fendo.2020.614692
  • Peer Reviewed / Open Access
• [Journal Article] FIB-4 First in the Diagnostic Algorithm of Metabolic-Dysfunction-Associated Fatty Liver Disease in the Era of the Global Metabodemic (2021)
  • Author(s): Sumida Y, Yoneda M, Tokushige K, Kawanaka M, Fujii H, Yoneda M, Imajo K, Takahashi H, Eguchi Y, Ono M, Nozaki Y, Hyogo H, Koseki M, Yoshida Y, Kawaguchi T, Kamada Y, Okanoue T, Nakajima A, Japan Study Group of NAFLD (JSG-NAFLD)
  • Journal Title: Life Volume: 11 Issue: 2 Pages: 143-143
  • DOI: 10.3390/life11020143
  • Peer Reviewed / Open Access
• [Journal Article] Marked effects of novel selective peroxisome proliferator-activated receptor α modulator, pemafibrate in severe hypertriglyceridemia: preliminary report (2020)
  • Author(s): Iitake Chie、Masuda Daisaku、Koseki Masahiro、Yamashita Shizuya
  • Journal Title: Cardiovascular Diabetology Volume: 19 Issue: 1 Pages: 201-206
  • DOI: 10.1186/s12933-020-01172-8
  • Peer Reviewed / Open Access
• [Journal Article] Progesterone receptor membrane associated component 1 enhances obesity progression in mice by facilitating lipid accumulation in adipocytes (2020)
  • Author(s): Furuhata Ryogo、Kabe Yasuaki、Kanai Ayaka、Sugiura Yuki、Tsugawa Hitoshi、Sugiyama Eiji、Hirai Miwa、Yamamoto Takehiro、Koike Ikko、Yoshikawa Noritada、Tanaka Hirotoshi、Koseki Masahiro、Nakae Jun、Matsumoto Morio、Nakamura Masaya、Suematsu Makoto
  • Journal Title: Communications Biology Volume: 3 Issue: 1 Pages: 479-479
  • DOI: 10.1038/s42003-020-01202-x
  • Peer Reviewed / Open Access
• [Journal Article] Evinacumab for Homozygous Familial Hypercholesterolemia (2020)
  • Author(s): Raal FJ, Kawashiri M, et al.
  • Journal Title: N Engl J Med. Volume: 383 Issue: 8 Pages: 711-720
  • DOI: 10.1056/nejmoa2004215
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serum Mac-2 Binding Protein Levels Associate with Metabolic Parameters and Predict Liver Fibrosis Progression in Subjects with Fatty Liver Disease: A 7-Year Longitudinal Study (2020)
  • Author(s): Kamada Yoshihiro、Morishita Koichi、Koseki Masahiro、Nishida Mayu、Asuka Tatsuya、Naito Yukiko、Yamada Makoto、Takamatsu Shinji、Sakata Yasushi、Takehara Tetsuo、Miyoshi Eiji
  • Journal Title: Nutrients Volume: 12 Issue: 6 Pages: 1770-1770
  • DOI: 10.3390/nu12061770
  • Peer Reviewed / Open Access
• [Journal Article] Loss of core fucosylation reduces low-density lipoprotein receptor expression in hepatocytes by inducing PCSK9 production (2020)
  • Author(s): Kamada Yoshihiro、Yamamoto Akiko、Fujiyoshi Anna、Koseki Masahiro、Morishita Koichi、Asuka Tatsuya、Takamatsu Shinji、Sakata Yasushi、Takehara Tetsuo、Taniguchi Naoyuki、Miyoshi Eiji
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 527 Issue: 3 Pages: 682-688
  • DOI: 10.1016/j.bbrc.2020.05.019
  • Peer Reviewed / Open Access
• [Journal Article] Antidiabetic Therapy in the Treatment of Nonalcoholic Steatohepatitis (2020)
  • Author(s): Sumida Yoshio、Yoneda Masashi、Tokushige Katsutoshi、Kawanaka Miwa、Fujii Hideki、Yoneda Masato
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 6 Pages: 1907-1907
  • DOI: 10.3390/ijms21061907
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia: A Global Call to Action. (2020)
  • Author(s): Representatives of the Global Familial Hypercholesterolemia Community,
  • Journal Title: JAMA Cardiol. Volume: - Issue: 2 Pages: 217-217
  • DOI: 10.1001/jamacardio.2019.5173
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Progranulin deficiency leads to enhanced age-related cardiac hypertrophy through complement C1q-induced β-catenin activation. (2020)
  • Author(s): Zhu Y, Ohama T, Kawase R, Chang J, Inui H, Kanno K, Okada T, Masuda D, Koseki M, Nishida M, Sakata Y, Yamashita S.
  • Journal Title: Journal of Molecular and Cellular Cardiology Volume: 138 Pages: 197-211
  • DOI: 10.1016/j.yjmcc.2019.12.009
  • Peer Reviewed / Open Access
• [Journal Article] Rivaroxaban Suppresses the Progression of Ischemic Cardiomyopathy in a Murine Model of Diet-Induced Myocardial Infarction (2019)
  • Author(s): Liu J, Nishida M, Inui H, Chang J, Zhu Y, Kanno K, Matsuda H, Sairyo M, Okada T, Nakaoka H, Ohama T, Masuda D, Koseki M, Yamashita S, Sakata Y.
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 26 Issue: 10 Pages: 915-930
  • DOI: 10.5551/jat.48405
  • NAID: 130007722198
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2019-10-01
  • Peer Reviewed / Open Access
• [Journal Article] Shotgun proteomic analysis reveals proteome alterations in HDL of patients with cholesteryl ester transfer protein deficiency. (2019)
  • Author(s): Okada T, Ohama T, Takafuji K, Kanno K, Matsuda H, Sairyo M, Zhu Y, Saga A, Kobayashi T, Masuda D, Koseki M, Nishida M, Sakata Y, Yamashita S.
  • Journal Title: J Clin Lipidol Volume: 印刷中 Issue: 2 Pages: 317-325
  • DOI: 10.1016/j.jacl.2019.01.002
  • Peer Reviewed / Open Access
• [Journal Article] Accelerated Atherogenicity in Tangier Disease (2018)
  • Author(s): Muratsu Jun、Koseki Masahiro、Masuda Daisaku、Yasuga Yuji、Tomoyama Satoki、Ataka Keiji、Yagi Yoshiki、Nakagawa Atsushi、Hamada Hidehumi、Fujita Shigeki、Hattori Hiroaki、Ohama Tohru、Nishida Makoto、Hiraoka Hisatoyo、Matsuzawa Yuji、Yamashita Shizuya
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 25 Issue: 10 Pages: 1076-1085
  • DOI: 10.5551/jat.43257
  • NAID: 130007490917
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2018-10-01
  • Peer Reviewed / Open Access
• [Journal Article] Effects of pemafibrate (K-877) on cholesterol efflux capacity and postprandial hyperlipidemia in patients with atherogenic dyslipidemia (2018)
  • Author(s): Yamashita Shizuya、Arai Hidenori、Yokote Koutaro、Araki Eiichi、Suganami Hideki、Ishibashi Shun
  • Journal Title: Journal of Clinical Lipidology Volume: 12 Issue: 5 Pages: 747-750
  • DOI: 10.1016/j.jacl.2018.06.010
  • Peer Reviewed / Open Access
• [Journal Article] A Novel Selective PPARα Modulator (SPPARMα), K-877 (Pemafibrate), Attenuates Postprandial Hypertriglyceridemia in Mice (2018)
  • Author(s): Masami Sairyo, Takuya Kobayashi, Daisaku Masuda, Koutaro Kanno, Yinghong Zhu, Takeshi Okada, Masahiro Koseki, Tohru Ohama, Makoto Nishida, Yasushi Sakata, Shizuya Yamashita
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 25 Issue: 2 Pages: 142-152
  • DOI: 10.5551/jat.39693
  • NAID: 130006328538
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed / Open Access
• [Journal Article] オキシステロールと動脈硬化 (2018)
  • Author(s): 小関正博
  • Journal Title: Heart View Volume: 22 Pages: 65-70
• [Journal Article] 小腸におけるコレステロール吸収と動脈硬化 (2018)
  • Author(s): 小関正博
  • Journal Title: Pharma Medica Volume: 36 Pages: 57-60
• [Presentation] Cardiac inflammation and dysfunction were accompanied with cholesterol-dominant steatohepatitis induced by atherogenic-diet (2021)
  • Author(s): Kanno K, Koseki M, Sakata Y
  • Organizer: Cardiovascular and Metabolic Week 2020
  • Int'l Joint Research
• [Presentation] High Fat Diet Containing 7-Ketocholesterol Induces Steatohepatitis and Cardiac Inflammation in STZ-Induced Diabetic Mice (2021)
  • Author(s): Masahiro Koseki、Juyang Chang、Kotaro Kanno、Ayami Saga、Hiroyasu Inui、Takeshi Okada、Shigeyoshi Saito、Tomoaki Higo、Seiko Ide、Katsunao Tanaka、Yinghong Zhu、Toru Ohhama、Makoto Nishida、Shizuya Yamashita、Yasushi Sakata
  • Organizer: 第85回日本循環器学会学術集会
• [Presentation] Progranulin Deficiency Leads to Enhanced Age-related Cardiac Hypertrophy through Complement C1q-induced Beta-catenin Activation (2021)
  • Author(s): Yinghong Zhu、Toru Ohama、Katsunao Tanaka、Kotaro Kanno、Jiuyang Chang、Hiroyasu Inui、Takeshi Okada、Masahiro Koseki、Makoto Nishida、Shizuya Yamashita、Yasushi Sakata
  • Organizer: 第85回日本循環器学会学術集会
• [Presentation] A dietary oxysterol, 7-ketocholesterol, exacerbates imiquimod-induced psoriasis-like dermatitis in steatohepatitis mice (2020)
  • Author(s): Saga A, Koseki M, Kanno K, Chang J, Asaji M, Okada T, Inui H, Zhu Y, Ohama T, Nishida M, Yamashita S, Sakata Y
  • Organizer: 日本研究皮膚科学会 第45回年次学術大会・総会
• [Presentation] Pemafibrate Suppresses Liver Inflammation Caused by Atherogenic Diet and Improves Cardiac Function. (2020)
  • Author(s): Kanno K, Koseki M, Saga A, Chang J, Okada T, Inui H, Asaji M, Zhu Y, Ohama T, Nishida M, Yamashita S, Sakata Y
  • Organizer: American Heart Association Scientific Sessions 2020
  • Int'l Joint Research
• [Presentation] Targeted Exon Sequencing of Lipid-Related Genes in Patients with Clinically Diagnosed Familial Hypercholesterolemia (2020)
  • Author(s): Okada T, Koseki M, Nishida M, Tanaka K, Inui H, Kanno K, Saga A, Ohama T, Kujiraoka T, Hattori H, Yamashita S, Sakata Y
  • Organizer: American Heart Association Scientific Sessions 2020
  • Int'l Joint Research
• [Presentation] Immunometabolic Disorder in Cardiovascular System and Liver Mediated by Long-term Exposure to Dietderived Oxidized Cholesterol, 7-Ketocholesterol (2020)
  • Author(s): Koseki M, Kanno K, Saga A, Chang J, Inui H, Okada T, Ohama T, Nishida M, Kamada Y, Miyoshi E, Yamashita S, Sakata Y
  • Organizer: Y 88th European Atherosclerosis Congress (EAS)
  • Int'l Joint Research
• [Presentation] Prevalence of Coronary Artery Disease and Achievement of Low-density Lipoprotein Cholesterol Management Targets in Familial Hypercholesterolemia Patients at Osaka University Hospital (2020)
  • Author(s): Okada T, Koseki M, Inui H, Kanno K, Saga A, Ohama T, Nishida M, Yamashita S, Sakata Y
  • Organizer: 88th European Atherosclerosis Congress (EAS)
  • Int'l Joint Research
• [Presentation] A Selective PPARα Modulator, Pemafibrate Reduced Hepatic Fibrosis and Cardiac Inflammation in Cholesterol-Dominant, Atherogenic-Diet Induced Steatohepatitis Model in STZ Induced Diabetic Mice. (2020)
  • Author(s): Chang J, Koseki M, Saga A, Kanno K, Okada T, Saito S, Kamada Y, Inui H, Asaji M, Zhu Y, Ohama T, Nishida M, Yamashita S, Sakata Y
  • Organizer: 第4回日本循環器学会基礎研究フォーラム（BCVR）
• [Presentation] Pemafibrate Improves Steatohepatitis and Cardiac Function in Atherogenic-diet Mice Model (2020)
  • Author(s): Kanno K, Koseki M, Saga A, Chang J, Okada T, Tanaka K, Inui H, Asaji M, Zhu Y, Ohama T, Nishida M, Yamashita S, Sakata Y
  • Organizer: 第4回日本循環器学会基礎研究フォーラム（BCVR）
• [Presentation] 食餌誘導性肝線維化モデルにおけるペマフィブラートの肝臓、心臓への作用メカニズムの解明 (2020)
  • Author(s): 小関正博, 冠野昂太郎, 常久洋, 嵯峨礼美, 岡田健志, 乾洋勉, 齋藤茂芳, 鎌田佳宏, 山下静也, 坂田泰史
  • Organizer: 第56回日本肝臓学会総会
  • Invited
• [Presentation] 食事由来酸化ステロール蓄積のNAFLD、動脈硬化の進展における影響 (2020)
  • Author(s): 小関正博, 三善英知, 西原利治
  • Organizer: 第56回日本肝臓学会総会
• [Presentation] The dietary 7-Ketocholesterol accelerated steatohepatitis in ob/ob mice by suppressing autophagy (2020)
  • Author(s): 常久洋, Koseki M, 嵯峨礼美
  • Organizer: 第56回日本肝臓学会総会
• [Presentation] イミキモド誘導乾癬モデルマウスにおける食事誘導脂肪肝炎の影響 (2020)
  • Author(s): 嵯峨礼美, 常久洋, 小関正博
  • Organizer: 第56回日本肝臓学会総会
• [Presentation] The Role of Th1 and Th17 During Myocardial Infarction and Inhibitory Effect of Probucol on Th1 in SR-BI KO/ApoeR61h/h Mice (2020)
  • Author(s): Inui H, Nishida M, Asaji M, Saga A, Kanno K, Okada T, Koseki M, Chang J, Zhu Y, Ohama T, Yamashita S, Sakata Y
  • Organizer: 第84回日本循環器学会学術集会
• [Presentation] A selective PPARα modulator, pemafibrate reduced hepatic cholesterol accumulation and inflammatory cell infiltration in atherogenic-diet induced steatohepatitis mouse model (2020)
  • Author(s): 冠野昂太郎, 小関正博, 嵯峨礼美, 常久洋, 岡田健志, 乾洋勉, 朝治真澄, 朱穎竑, 大濱透, 西田誠, 山下静也, 坂田泰史
  • Organizer: 第84回日本循環器学会学術集会
• [Presentation] The Current Status of Achievement of Low-density Lipoprotein Cholesterol Management Targets in Familial Hypercholesterolemia Patients in Osaka University Hospital (2020)
  • Author(s): Okada T, Koseki M, Inui H, Kanno K, Chang J, Zhu Y, Saga A, Asaji M, Ohama T, Nishida M, Yamashita S, Sakata Y
  • Organizer: 第84回日本循環器学会学術集会
• [Presentation] 動脈硬化惹起食誘導脂肪肝炎モデルにおける、ペマフィブラートの抗脂肪肝炎、抗心筋炎症作用の解明 (2020)
  • Author(s): 小関正博、冠野昂太郎、常久洋、嵯峨礼美、岡田健志、鎌田佳宏、山下静也、坂田泰史
  • Organizer: 第52回日本動脈硬化学会総会・学術集会
  • Invited
• [Presentation] NAFLD/NASH、動脈硬化進展における外因性酸化ステロール7-ketocholesterolの影響 (2020)
  • Author(s): 小関正博, 冠野昂太郎, 常久洋, 嵯峨礼美, 岡田健志, 乾洋勉, 鎌田佳宏, 山下静也, 坂田泰史
  • Organizer: 第52回日本動脈硬化学会総会・学術集会
  • Invited
• [Presentation] 食餌誘発性脂肪肝炎マウスモデルにおいて7-ketocholesterolはイミキモド誘導乾癬様皮膚炎を増悪させる (2020)
  • Author(s): 嵯峨礼美, 小関正博, 冠野昂太郎, 常久洋, 朝治真澄, 岡田健志, 鎌田佳宏, 乾洋勉, 朱穎竑, 大濵透, 西田誠, 山下静也, 坂田泰史
  • Organizer: 第52回日本動脈硬化学会総会・学術集会
• [Presentation] The Dietary 7-ketocholesterol Accelerated Steatohepatitis in STZ Induced Diabetic Mice (2020)
  • Author(s): Chang J, Koseki M, Saga A, Kanno K, Okada T, Saito S, Kamada Y, Inui H, Asaji M, Zhu Y, Ohama T, Nishida M, Yamashita S, Sakata Y
  • Organizer: 第52回日本動脈硬化学会総会・学術集会
• [Presentation] Progranulin deficiency leads to enhanced age-related cardiac hypertrophy through Clq-induced β-catenin activation (2020)
  • Author(s): 朱穎竑, 大濵透, 常久洋, 乾洋勉, 冠野昂太郎, 岡田健志, 小関正博, 西田誠, 坂田泰史, 山下静也
  • Organizer: 第52回日本動脈硬化学会総会・学術集会
• [Presentation] A selective PPARα modulator, pemafibrate reduced hepatic cholesterol content and inflammatory cell infiltration in atherogenic-diet induced steatohepatitis mouse model (2020)
  • Author(s): Kanno K, Koseki M, Saga A, Chang J, Okada T, Inui H, Asaji M, Zhu Y, Ohama T, Nishida M, Yamashita S, Sakata Y.
  • Organizer: Keystone Symposia 2020
  • Int'l Joint Research
• [Presentation] Pemafibrate improves hepatic fibrosis and cardiac inflammation in atherogenic diet-induced steatohepatitis mice model (2020)
  • Author(s): Koseki M
  • Organizer: Keystone Symposia 2020
  • Int'l Joint Research
• [Presentation] コレステリルエステル転送蛋白(CETP)欠損症リポ蛋白の動脈硬化惹起性に関する検討 (2020)
  • Author(s): 岡田健志、大濱透、乾洋勉、冠野昂太郎、小関正博、西田誠、山下静也、坂田泰史
  • Organizer: 第54回日本成人病（生活習慣病）学会学術集会
• [Presentation] 当科脂質外来における家族性高コレステロール血症診療の現状 (2020)
  • Author(s): 岡田健志、小関正博、西田誠、冠野昂太郎、乾洋勉、嵯峨礼美、大濱透、山下静也、坂田泰史
  • Organizer: 第54回日本成人病（生活習慣病）学会学術集会
• [Presentation] 著明な低HDLコレステロール血症をきたす原発性脂質異常症の臨床的特徴と鑑別 (2020)
  • Author(s): 小関正博、岡田健志、冠野昂太郎、乾洋勉、大濱透、西田誠、坂田泰史
  • Organizer: 第54回日本成人病（生活習慣病）学会学術集会
• [Presentation] 著明な高トリグリセリド血症をきたす原発性脂質異常症に対する食事療法と薬物療法 (2020)
  • Author(s): 小関正博、岡田健志、大濱透、西田誠、坂田泰史
  • Organizer: 第54回日本成人病（生活習慣病）学会学術集会
• [Presentation] 脂質の違いが引き起こすImmunometabolic Disorders－動脈硬化症とNAFLD/NASH－ (2020)
  • Author(s): 小関正博、冠野昂太郎、常久洋、嵯峨礼美、乾洋勉、岡田健志、大濱透、西田誠、坂田泰史
  • Organizer: 第54回日本成人病（生活習慣病）学会学術集会
• [Presentation] 当院通院中の肥満患者に対する運動習慣・体組成・心不全転帰の現状 (2020)
  • Author(s): 佐藤慶彦、岩田昌美、山本大貴、西佳奈美、中村奈津美、浅井優希、竹入沙知、早川麻理子、小関正博、前田和久
  • Organizer: 日本心臓リハビリテーション学会 第5回近畿地方会
• [Presentation] The Current Status of the Treatment of FH Patients and the Achievement of LDL-C Target Value in the Lipid Clinic in Osaka University Hospital (2019)
  • Author(s): Koseki M, Okada T, Kanno K, Ohama T, Nishida M, Yamashita S, Sakata Y.
  • Organizer: FH Global Summit 2019
  • Int'l Joint Research
• [Presentation] Pemafibrate regulate intestinal lipid absorption in diet-induced nonalcoholic steatohepatitis model in mice (2019)
  • Author(s): Kanno K, Koseki M, Saga A, Chang J, Okada T, Inui H, Asaji M, Zhu Y, Ohama T, Nishida M, Yamashita S, Sakata Y.
  • Organizer: American Heart Association's Scientific Sessions 2019
  • Int'l Joint Research
• [Presentation] The Predominance of Th1 and Th17 During the Process of Myocardial Infarction in Non-surgical MI model, SR-BI KO/ApoeR61h/h mice (2019)
  • Author(s): Inui H, Nishida M, Asaji M, Saga A, Kanno K , Chang J, Zhu Y , Okada T, Ohama T , Koseki M, Yamashita S, Sakata Y.
  • Organizer: American Heart Association's Scientific Sessions 2019
  • Int'l Joint Research
• [Presentation] Pgrn Suppresses Pressure Overload-induced Cardiac Hypertrophy And Heart Failure In Mice Via Inhibiting The Activation Of β-catenin (2019)
  • Author(s): Zhu Y, Ohama T, Inui H, Kanno K, Chang J, Okada T, Koseki M, Nishida M, Sakata Y, Yamashita S.
  • Organizer: American Heart Association's Scientific Sessions 2019
  • Int'l Joint Research
• [Presentation] 7-ketocholesterolへの長期曝露により増悪する Immunometabolic Disorders -動脈硬化、脂肪肝炎、乾癬- (2019)
  • Author(s): 小関正博、冠野昂太郎、常久洋、嵯峨礼美、岡田健志、乾洋勉、朝治真澄、鎌田佳宏、大濵透、西田誠、山下静也、坂田泰史
  • Organizer: CVMW2019
  • Invited
• [Presentation] Prevalence of Coronary Artery Disease and Achievement of Low-density Lipoprotein Cholesterol Management Targets in Familial Hypercholesterolemia Patients at Osaka University Hospital (2019)
  • Author(s): Okada T, Koseki M, Inui H, Kanno K, Sakata Y
  • Organizer: CVMW2019
• [Presentation] Steatohepatitis mediated by the dietary cholesterol, 7-ketochlesterol accelerated atherosclerosis in Ldlr deficient mice (2019)
  • Author(s): Kanno K, Koseki M, Jiuyang C, Inui H, Okada T, Sakata Y
  • Organizer: CVMW2019
• [Presentation] The role of Th1 and Th17 During Acute phase of Myocardial Infarction in SR-BI KO/ApoeR61h/h mice (2019)
  • Author(s): Inui H, Koseki M, Kanno K, Okada T, Sakata Y
  • Organizer: CVMW2019
• [Presentation] 著明な高LDL-C血症をきたした二症例における食事指導の重要性に関する考察 (2019)
  • Author(s): 小関正博、岡田健志、坂田泰史
  • Organizer: 第33回小児脂質研究会
• [Presentation] NAFLD/NASH進展における外因性酸化ステロールの影響の検討 (2019)
  • Author(s): 小関正博、鎌田佳宏、小野正文、嵯峨礼美、冠野昂太郎、常久洋、乾洋勉、岡田健志、大濵透、西田誠、山田眞、三善英知、坂田泰史、山下静也、西原利治
  • Organizer: 第51回日本動脈硬化学会総会・学術集会
  • Invited
• [Presentation] 高コレステロール食誘発心筋梗塞モデルマウスにおけるT細胞の関与の検討 (2019)
  • Author(s): 乾洋勉、劉静一、西田誠、常久洋、朱頴広、冠野昂太郎、松田響、岡田健志、大濵透、小関正博、山下静也
  • Organizer: 第51回日本動脈硬化学会総会・学術集会
• [Presentation] 乾癬様皮膚炎マウスモデルにおける外因性酸化ステロールの影響の検討 (2019)
  • Author(s): 嵯峨礼美、小関正博、冠野昂太郎、常久洋、朝治真澄、岡田健志、乾洋勉、朱頴広、大濵透、西田誠、山下静也、坂田泰史
  • Organizer: 第51回日本動脈硬化学会総会・学術集会
• [Presentation] 新規食餌誘導性非アルコール性脂肪肝炎マウスモデルにおけるPemafibrateの作用機序の検討 (2019)
  • Author(s): 冠野昂太郎、小関正博、嵯峨礼美、常久洋、岡田健志、乾洋勉、朝治真澄、朱頴広、大濵透、西田誠、山下静也、坂田泰史
  • Organizer: 第51回日本動脈硬化学会総会・学術集会
• [Presentation] 当科脂質外来における家族性高コレステロール血症診療の現状 (2019)
  • Author(s): 岡田健志、小関正博、西田誠、冠野昂太郎、乾洋勉、嵯峨礼美、朝治真澄、大濵透、服部浩明、山下静也、坂田泰史
  • Organizer: 第51回日本動脈硬化学会総会・学術集会
• [Presentation] The effect of dietary oxysterol on steatohepatitis in diabetic mice model (2019)
  • Author(s): Chang J, Koseki M, Saga A, Kanno K, Okada T, Asaji M, Zhu Y, Liu J, Matsuda H, Masuda D, Ohama T, Nishida M, Yamashita S, Sakata Y.
  • Organizer: 第51回日本動脈硬化学会総会・学術集会
• [Presentation] Development of an Enzyme-Linked Immunosorbent Assay for Oxidized High Density Lipoprotein and Its Clinical Application for Cardiovascular Risk Assessment (2019)
  • Author(s): Okada T, Yamashita S, Ohama T, Inui H, Kanno K, Koseki M, Nishida M, Sakata Y.
  • Organizer: 第3回日本循環器学会基礎研究フォーラム
• [Presentation] The dietary oxidized cholesterol, 7-ketocholesterol, accelerated steatohepatitis and atherosclerosis in Ldlr deficient mice model (2019)
  • Author(s): Kanno K, Koseki M, Saga A, Chang J, Okada T, Inui H, Asaji M, Zhu Y, Ohama T, Nishida M, Yamashita S, Sakata Y.
  • Organizer: 第3回日本循環器学会基礎研究フォーラム
• [Presentation] The Predominance of Th1 and Th17 During the Process of Myocardial Infarction in Non-surgical MI model, SR-BI KO/ApoeR61h/h mice (2019)
  • Author(s): Inui H, Nishida M, Chang J, Zhu Y, Kanno K, Okada T, Ohama T, Koseki M, Yamashita S, Sakata Y.
  • Organizer: 第3回日本循環器学会基礎研究フォーラム
• [Presentation] The dietary oxysterol accelerated steatohepatitis in ob/ob mice model (2019)
  • Author(s): Chang J, Koseki M, Saga A, Kanno K, Okada T, Inui H, Asaji M, Zhu Y, Ohama T, Nishida M, Yamashita S, Sakata Y.
  • Organizer: 第3回日本循環器学会基礎研究フォーラム
• [Presentation] Oxidized cholesterol, 7-ketocholesterol, is an Important Risk Factor for the Development of Atherosclerosis (2019)
  • Author(s): Masahiro Koseki
  • Organizer: 第83回日本循環器学会学術集会
• [Presentation] Establishment of an Enzyme-Linked Immunosorbent Assay for Oxidized High Density Lipoprotein and Its Clinical Significance for Cardiovascular Risk Assessment (2019)
  • Author(s): Takeshi Okada, Tohru Ohama, Mitsuyo Okazaki, Hiroyasu Inui, Kotaro Kanno, Hibiki Matsuda, Yinghong Zhu, Daisaku Masuda, Masahiro Koseki, Makoto Nishida, Yasushi Sakata, Shizuya Yamashita
  • Organizer: 第83回日本循環器学会学術集会
• [Presentation] Lipoprotein Particle Number Analysis of Detailed Subclasses by Gel Permeation HPLC (2018)
  • Author(s): Takeshi Okada, Tohru Ohama, Hiroyasu Inui, Kotaro Kanno, Hibiki Matsuda, Yinghong Zhu, Daisaku Masuda, Masahiro Koseki, Makoto Nishida, Yasushi Sakata, Shizuya Yamashita
  • Organizer: Gordon Research Conference 2018 Lipoprotein Metabolism
  • Int'l Joint Research
• [Presentation] Atherogenicity in Tangier Disease - Literature-based Analysis and A Case Report- (2018)
  • Author(s): Masahiro Koseki, Shizuya Yamashita,Yasushi Sakata
  • Organizer: Gordon Research Conference 2018 Lipoprotein Metabolism
  • Int'l Joint Research
• [Presentation] Adipose Tissue-derived Cell Transplantation In A Homozygous Familial Hypercholesterolemia Patient (2018)
  • Author(s): Masahiro Koseki, Ayami Saga, Takeshi Okada, Kotaro Kanno, Masumi Asaji, Kouichi Tomita, Keigo Osuga, Sachiko Ezoe, Makoto Nishida, Yasushi Sakata, Shizuya Yamashita
  • Organizer: American Heart Association Annual Meeting 2018
  • Int'l Joint Research
• [Presentation] The Molecular Mechanism Underlying both Atherosclerosis and Non-alcoholic Steatohepatitis (2018)
  • Author(s): Masahiro Koseki, Shizuya Yamashita,Yasushi Sakata
  • Organizer: 第66回日本心臓病学会学術集会
  • Invited
• [Presentation] 腸管上皮細胞のコレステロールトランスポータ―NPC1L1と核内受容体LXRを識る (2018)
  • Author(s): 小関正博、嵯峨礼美、冠野昂太郎、岡田健志、大濱透、西田誠、山下静也、坂田泰史
  • Organizer: 第50回日本動脈硬化学会総会学術集会
  • Invited
• [Presentation] 家族性高コレステロール血症ホモ接合体に対する同種脂肪組織由来幹細胞移植療法の開発の現状 (2018)
  • Author(s): 小関正博、嵯峨礼美、冠野昂太郎、岡田健志、朝治真澄、冨田興一、大須賀慶悟、江副幸子、西田誠、坂田泰史、山下静也
  • Organizer: 第50回日本動脈硬化学会総会学術集会
  • Invited
• [Presentation] NAFLD/NASHと動脈硬化症をつなぐ分子メカニズムは何か (2018)
  • Author(s): 小関正博、嵯峨礼美、冠野昂太郎、岡田健志、山下静也、坂田泰史
  • Organizer: 第50回日本動脈硬化学会総会学術集会
  • Invited
• [Presentation] LXRalphaの新規調節機構：TTC39B阻害はLXRalphaのユビキチン化によるプロテアソーム分解を減弱させアテローム性動脈硬化症および非アルコール性脂肪性肝炎の両方を改善する (2018)
  • Author(s): 小関正博、山下静也、坂田泰史
  • Organizer: 第55回日本臨床分子医学会学術集会
• [Presentation] Lipoprotein Particle Number Analysis of Detailed Subclasses by Gel Permeation HPLC (2018)
  • Author(s): Takeshi Okada, Tohru Ohama, Mitsuyo Okazaki, Hiroyasu Inui, Kotaro Kanno, Hibiki Matsuda, Yinghong Zhu, Daisaku Masuda, Masahiro Koseki, Makoto Nishida, Yasushi Sakata, Shizuya Yamashita
  • Organizer: 第66回日本心臓病学会学術集会
• [Presentation] 重症家族性高コレステロール血症に対する再生医療の臨床応用 (2018)
  • Author(s): 冠野昂太郎、小関正博、嵯峨礼美、岡田 健志、朝治真澄、冨田興一、大須賀慶悟、江副幸子、西田誠、坂田泰史、山下 静也
  • Organizer: 第50回日本動脈硬化学会総会・学術集会
• [Presentation] Accelerated Systematic Atherogenicity in Tangier Disease -Review and Case Report- (2018)
  • Author(s): Jun Muratsu, Masahiro Koseki, Daisaku Masuda, Yuji Yasuga, Satoki Tomoyama, Keiji Ataka, Yoshiki Yagi, Atsushi Nakagawa, Hidehumi Hamada, Shigeki Fujita, Tohru Ohama, Makoto Nishida, Hisatoyo Hiraoka, Yuji Matsuzawa, Shizuya Yamashita
  • Organizer: 第50回日本動脈硬化学会総会・学術集会
• [Presentation] 冠動脈硬化と頸動脈分岐部狭窄を来した弾性繊維性仮性黄色腫の1例 (2018)
  • Author(s): 冠野昂太郎、小関正博、乾洋勉、松田 響、西良雅己、岡田健志、増田大作、 大濱透、西田誠、室田浩之、山下静也
  • Organizer: 第50回日本動脈硬化学会総会・学術集会
• [Remarks] 大阪大学 大学院医学系研究科 循環器内科学循環器脂質・動脈硬化グループ
  • URL: http://www.cardiology.med.osaka-u.ac.jp/?page_id=33160
• [Remarks] 家族性高コレステロール血症 大阪大学 大学院医学系研究科 循環器内科学 循環器脂質・動脈硬化研究室
  • URL: http://fh-osaka-univ.org/
• [Remarks] 動脈硬化性疾患高リスク病態におけるコレステロール吸収・合成マーカー(CACHE研究)
  • URL: http://www.cardiology.med.osaka-u.ac.jp/?post_type=clinical
• [Remarks] 匂い解析定量化技術を用いた心不全バイオマーカーの探索的研究
  • URL: http://www.cardiology.med.osaka-u.ac.jp/?post_type=clinical
• [Remarks] 原発性脂質異常症の予後実態調査(PROLIPID研究)
  • URL: http://www.cardiology.med.osaka-u.ac.jp/?post_type=clinical