Faculty Profiles - OHISHI Mitsuru

Papers - OHISHI Mitsuru

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Wang Xiang, Sugimoto Ken, Fujisawa Tomomi, Shindo Nobuyasu, Minato Satomi, Kamada Yoshihiro, Hamano Mina, Ohishi Mitsuru, Ikegami Hiroshi, Rakugi Hiromi . 脂肪肝シオノギ系マウスの非アルコール性脂肪性肝疾患の発症を阻害するエゼチミブの新規の作用(Novel effect of ezetimibe to inhibit the development of non-alcoholic fatty liver disease in Fatty Liver Shionogi mouse) . Hepatology Research44 ( 1 ) 102 - 113 2014.1

Language：English Publisher：John Wiley & Sons Australia, Ltd

エゼチミブが非アルコール性脂肪性肝疾患(NAFLD)の発症を抑制するかどうか明らかにし、その機序をNAFLD/非アルコール性脂肪性肝炎の自然発症モデルである脂肪肝シオノギ(FLS)系マウスを用いて解析した。20週齢の雄のFLS系マウスを2群に分割した(各7匹)。標準食であるCRF-1、またはCRF-1に0.005%(w/w)のエゼチミブ(1日7mg/kg)を4週間投与した。エゼチミブ投与の4週後に画分のマウスの組織学的な分析を行い分子機序について解析を行った。その結果、エゼチミブの摂取により標準食を摂取したマウスでは肝脂肪症と線維症の改善が見られた。エゼチミブは肝臓の活性酸素種の生成を抑制し、Skp2とCDC20のタンパク質量の低下を介して超低密度リポタンパク質の集合と輸送のための重要な分子であるミクロソームのトリグリセリド輸送タンパク質(MTP)のユビキチン化とタンパク質の分解を抑制した。以上の結果から、エゼチミブは肝臓における脂質の合成を低下させるだけでなく、肝臓からの脂質の放出を促進することが明らかとなり、この機序には肝臓の活性酸素種の生成の抑制を介したMTPの翻訳後の分解抑制が関与し、NAFLDの発症が防止されると考えられた。

茶圓秀人, 湯淺敏典, 植屋奈美, 堀添善尚, 川添晋, 窪田佳代子, 水上尚子, 高崎州亜, 木佐貫彰, 大石充 . 成人期まで外科的介入なく経過したShone症候群の一例 . 超音波医学41 ( 1 ) 93 - 93 2014.1

MIYATA Masaaki, AKASAKI Yuichi, MIYAUCHI Takahiro, IKEDA Yoshiyuki, OHISHI Mitsuru . 02-2 Preventive effect of thermal therapy on heart failure due to pressure overload . The Journal of The Japanese Society of Balneology, Climatology and Physical Medicine77 ( 5 ) 426 - 426 2014

Language：English Publisher：The Japanese Society of Balneology, Climatology and Physical Medicine

Introduction: Long-term cardiac hypertrophy causes heart failure. One of the mechanisms of this transition from hypertrophy to heart failure is collapse of hypoxic response and angiogenesis. Heat shock protein 27 (HSP27) was found to act as an anti-apoptotic protein and its phosphorylation is responsible for the protection of cells against heat stress. HSP27 has been reported to regulate p53 expression, which contributes to down-regulate angiogenic factors through hypoxia inducible factor-1α(HIF-1α). We have reported that thermal therapy, namely Waon therapy, improves cardiac and vascular function in patients with chronic heart failure. However, the effect of this therapy on cardiac hypertrophy due to pressure overload is unknown. The purpose of this study is to investigate the effects and mechanisms of thermal therapy (Waon therapy) on the transition from cardiac hypertrophy to heart failure after pressure overload. Methods: Cardiac hypertrophy was induced by transverse aortic constriction (TAC) in C57BL/6 mice. At 2 weeks after TAC, all mice were examined by echocardiography and showed left ventricular hypertrophy. Then, mice were randomly divided into thermal therapy or untreated group. Thermal therapy group received thermal therapy using an experimental far infrared ray dry sauna, which elevates the core temperature by 1 degree Celsius for 30 minutes, daily for 4 weeks. Sham operated mice were used as control. At 6 weeks after TAC, we measured body weight, heart rate and blood pressure before sacrifice, and eviscerated heart and leg muscle. Western blot analysis of p53, phosphorylated HSP27, HIF-1α and vascular endothelial growth factor (VEGF) was performed using extracted protein form heart. Results: At 6 weeks after TAC, body weight, heart rate and blood pressure did not differ in three groups. Echocardiography showed that left ventricular fractional shortening of thermal therapy group was significantly larger than that of untreated group (Sham vs. Untreated vs. Thermal; 50.0±1.7 vs. 36.7±1.3 vs. 46.2±0.5, P<0.01, n=6 each). Heart weight/tibia length ratio of thermal therapy group was significantly smaller than that of untreated group (6.7±0.1 vs. 9.7±0.5 vs. 7.9±0.2, P<0.01, n=9 each). Western blot showed that thermal therapy increased phosphorylation of HSP27 and reduced p53. Thermal therapy also increased HIF-1α and VEGF at 6 weeks after TAC. Capillary/myofiber ratio was larger in thermal therapy group than that in untreated group (1.71±0.05 vs. 2.04±0.04 vs. 2.41±0.10, P<0.01, n=4 each). Conclusion: Thermal therapy, namely Waon therapy, prevented the transition from cardiac hypertrophy to heart failure induced by pressure overload in mice. As the mechanism, thermal therapy amplified the phosphorylation of HSP27 and inhibited p53, increased HIF-1α and VEGF, and then increased angiogenesis.

DOI： 10.11390/onki.77.426

CiNii Research

Kamide K, Asayama K, Katsuya T, Ohkubo T, Hirose T, Inoue R, Metoki H, Kikuya M, Obara T, Hanada H, Thijs L, Kuznetsova T, Noguchi Y, Sugimoto K, Ohishi M, Morimoto S, Nakahashi T, Takiuchi S, Ishimitsu T, Tsuchihashi T, Soma M, Higaki J, Matsuura H, Shinagawa T, Sasaguri T, Miki T, Takeda K, Shimamoto K, Ueno M, Hosomi N, Kato J, Komai N, Kojima S, Sase K, Miyata T, Tomoike H, Kawano Y, Ogihara T, Rakugi H, Staessen JA, Imai Y. . Genome-Wide Pharmacogenomic Response to antihypertensive medication using home blood pressure measurements: a pilot study nested within the HOMED-BP Study. . Pharmacogenomics 14 ( 14 ) 1709 - 1721 2013.11Reviewed

Kawai T, Ohishi M, Takeya Y, Onishi M, Ito N, Oguro R, Yamamoto K, Kamide K, Rakugi H. . Carotid Plaque Score and Intima Media Thickness as Predictors of Stroke and Mortality in Hypertensive Patients. . Hypertens Res 36 902 - 909 2013.7Reviewed

Ohishi M, Kawai T, Hayashi N, Kitano S, Katsuya T, Nagano M, Hirotani A, Yamamoto K, Kamide K, Rakugi H. . Effect of tablets with a combination of telmisartan and amlodipine on patients with hypertension: The Cotalo study. . Hypertens Res 36 ( 7 ) 620 - 626 2013.7Reviewed

Kawai T, Ohishi M, Ito N, Onishi M, Takeya Y, Yamamoto K, Kamide K, Rakugi H. . Alteration of Vascular Function is Important Factor in the Correlation between Visit-to-visit Variability in Blood Pressure and Cardiovascular Disease. . J Hypertens 31 ( 7 ) 1387 - 1395 2013.7Reviewed

Takeuchi K, Yamamoto K, Ohishi M, Takeshita K, Hongyo K, Kawai T, Takeda M, Kamide K, Kurtz TW, Rakugi H . Telmisartan modulates mitochondrial function in vascular smooth muscle cells . Hypertens Res36 ( 5 ) 433 - 439 2013.5Reviewed

Kawai T, Ohishi M, Kamide K, Nakama C, Onishi M, Ito N, Takami Y, Takeya Y, Rakugi H. . Differences between daytime and night-time blood pressure variability regarding systemic atherosclerotic change and renal function . Hypertens Res36 ( 3 ) 232 - 239 2013.3Reviewed

Takeda M, Yamamoto K, Takemura Y, Takeshita H, Hongyo K, Kawai T, Hanasaki-Yamamoto H, Oguro R, Takami Y, Tatara Y, Takeya Y, Sugimoto K, Kamide K, Ohishi M, Rakugi H. . Loss of Angiotensin-converting enzyme 2 exaggerates high-calorie diet-induced insulin resistance by reduction of GLUT4 in mice. . Diabetes62 ( 1 ) 223 - 233 2013.1Reviewed

Kawai T, Ohishi M, Onishi M, Ito N, Takeya Y, Maekawa Y, Rakugi H . Cut-off Value of Brachial-ankle Pulse Wave Velocity to Predict Cardiovascular Disease in Hypertensive Patients: A Cohort Study. . J Atheroscler Thromb 20 ( 4 ) 391 - 400 2013Reviewed

Kawai T, Ohishi M, Takeya Y, Onishi M, Ito N, Yamamoto K, Oguro R, Kamide K, Rakugi H. . Adioponectin single nucleotide polymorphism is a genetic risk factor for stroke through high pulse wave pressure: a cohort study. . J Atheroscler Thromb 20 ( 2 ) 152 - 160 2013Reviewed

Kawai T, Kamide K, Ito N, Onishi M, Oguro R, Takeya Y, Tatara Y, Maekawa Y, Katsuya T, Ohishi M, Rakugi H. . -374 T/A polymorphism in RAGE gene is associated with onset of diabetes mellitus, atherosclerosis, and renal dysfunction in patients with hypertension . Clin Exp Hypertens 35 ( 3 ) 236 - 241 2013Reviewed

Kawai T, Ohishi M, Onishi M, Takeya Y, Ito N, Kato N, Yamamoto K, Kamide K, Rakugi H. . Influence of renin angiotensin system gene polymorphisms on visit-to-visit blood pressure variability in hypertensive patients. . Am J Hypertens25 ( 12 ) 1249 - 1255 2012.12Reviewed

Kawai T, Ohishi M, Takeya Y, Onishi M, Ito N, Yamamoto K, Kamide K, Rakugi H. . Serum uric acid is an independent risk factor for cardiovascular disease and mortality in hypertensive patients. . Hypertens Res35 ( 11 ) 1087 - 1092 2012.11Reviewed

Kawai T, Kamide K, Onishi M, Hongyo K, Yamamoto-Hanasaki H, Oguro R, Maekawa Y, Yamamoto K, Takeya Y, Sugimoto K, Ohishi M, Rakugi H. . Relationship between renal hemodynamic status and aging in patients without diabetes evaluated by renal doppler ultrasonography. . Clin Exp Nephr16 ( 5 ) 786 - 791 2012.10Reviewed

Kainuma S, Taniguchi K, Daimon T, Sakaguchi T, Funatsu T, Miyagawa S, Kondoh H, Takeda K, Shudo Y, Masai T, Ohishi M, Sawa T. . Mitral valve repair for medically refractory functional mitral regurgitation in patients with end-stage renal disease and advanced heart failure. . Circulation126 ( 11 Suppl 1 ) S205 - S213 2012.9Reviewed

Congrains A, Kamide K, Katsuya T, Yasuda O, Oguro R, Yamamoto K, Ohishi M, Rakugi H. . CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC. . Biochem Biophys Res Commun419 ( 4 ) 612 - 616 2012.3Reviewed

Kawai T, Ohishi M, Kamide K, Onishi M, Takeya Y, Tatara Y, Oguro R, Yamamoto K, Sugimoto K, Rakugi H. . The impact of visit-to-visit variability in blood pressure on renal function. . Hypertens Res35 ( 2 ) 239 - 243 2012.2Reviewed

Congrains CA, Kamide K, Oguro R, Yasuda O, Miyata K, Yamamoto E, Kawai T, Kusunoki H, Yamamoto H, Takeya Y, Yamamoto K, Onishi M, Sugimoto K, Katsuya T, Awata N, Ikebe K, Gondo Y, Oike Y, Ohishi M, Rakugi H. . Genetic Variants at the 9q21 locus contribute to atherosclerosis through modulation of ANRIL and CDKN2A/B. . Atherosclerosis220 ( 2 ) 449 - 455 2012.2Reviewed

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