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野間 貴久 ノマ タカヒサ

所属
医学部
医学科
職名准教授
Last Updated :2020/09/17

研究者基本情報

学歴

  • 1996年04月 - 2000年03月, 香川医科大学大学院
  • 1990年04月 - 1996年03月, 香川医科大学, 医学部

学位

  • 医学博士, 香川医科大学

経歴

  •   2003年04月,  - 2007年03月, 香川医科大学医学部附属病院附属病院, 第二内科, 助手
  •   2003年07月,  - 2006年06月, DUKE University Medical Center
  •   1996年04月,  - 2003年03月, 香川医科大学医学部附属病院, 第二内科, 医員

研究活動情報

研究分野

  • ライフサイエンス / 循環器内科学

研究キーワード

    心不全

Misc

  • Valsartan ameliorates the constitutive adipokine expression pattern in mature adipocytes: a role for inverse agonism of the angiotensin II type 1 receptor in obesity, Arif U. Hasan, Koji Ohmori, Takeshi Hashimoto, Kazuyo Kamitori, Fuminori Yamaguchi, Yasuhiro Ishihara, Naoko Ishihara, Takahisa Noma, Masaaki Tokuda, Masakazu Kohno, HYPERTENSION RESEARCH, 37, (7), 621 - 628,   2014年07月, [査読有り]
    Angiotensin (Ang) II receptor blockers (ARBs) alleviate obesity-related insulin resistance, which suggests an important role for the Ang II type 1 receptor (AT1R) in the regulation of adipocytokines. Therefore, we treated mature 3T3-L1 adipocytes with 50 mu mol l(-1) of valsartan, a selective AT1R blocker without direct agonism to peroxisome proliferator-activated receptor (PPAR)-gamma. In the absence of effective concentrations of Ang II, unstimulated mature adipocytes expressed and secreted high levels of interleukin (IL)-6. This constitutive proinflammatory activity was attenuated by the suppression of extracellular signal-regulated kinase phosphorylation by valsartan but was unaffected by the Ang II type 2 receptor blocker PD123319. COS7 cells co-transfected with AT1R and IL-6, which expressed NF-kappa B but lacked PPAR-gamma, showed no constitutive but substantial ligand-dependent IL-6 reporter activity, which was counteracted by valsartan. Valsartan preserved cytosolic I kappa B-alpha and subsequently reduced nuclear NF-kappa B1 protein expression in mature adipocytes. Interestingly, valsartan did not increase PPAR-gamma messenger RNA expression per se but enhanced the transcriptional activity of PPAR-gamma in mature adipocytes; this enhancement was accompanied by upregulation of the PPAR coactivator (PGC)-1 alpha. Moreover, T0090907, a PPAR-gamma inhibitor, increased IL-6 expression, and this increase was attenuated by valsartan. Indeed, addition of valsartan without direct PPAR-gamma agonism increased adiponectin production in mature adipocytes. Together, the findings indicate that valsartan blocks the constitutive AT1R activity involving the NF-kappa B pathway that limits PPAR-gamma activity in mature adipocytes. Thus, inverse agonism of AT1R attenuates the spontaneous proinflammatory response and enhances the constitutive insulin-sensitizing activities of mature adipocytes, which may underlie the beneficial metabolic impacts of ARBs.
  • Prognostic value of circulating regulatory T cells for worsening heart failure in heart failure patients with reduced ejection fraction., 野間貴久, 岡本尚子, 石原靖大, 宮内友香, 高畠渉, 石澤真, 難波経立, 村上和司, 岩藤泰慶, 大森浩二, 河野雅和, International Heart Journal, 55, (3), 271-277,   2014年05月, [査読有り]
  • Renal Sympathetic Denervation Suppresses De Novo Podocyte Injury and Albuminuria in Rats With Aortic Regurgitation, Kazi Rafiq, Takahisa Noma, Yoshihide Fujisawa, Yasuhiro Ishihara, Yoshie Arai, A. H. M. Nurun Nabi, Fumiaki Suzuki, Yukiko Nagai, Daisuke Nakano, Hirofumi Hitomi, Kento Kitada, Maki Urushihara, Hiroyuki Kobori, Masakazu Kohno, Akira Nishiyama, CIRCULATION, 125, (11), 1402 - U178,   2012年03月, [査読有り]
    Background-The presence of chronic kidney disease is a significant independent risk factor for poor prognosis in patients with chronic heart failure. However, the mechanisms and mediators underlying this interaction are poorly understood. In this study, we tested our hypothesis that chronic cardiac volume overload leads to de novo renal dysfunction by coactivating the sympathetic nervous system and renin-angiotensin system in the kidney. We also examined the therapeutic potential of renal denervation and renin-angiotensin system inhibition to suppress renal injury in chronic heart failure. Methods and Results-Sprague-Dawley rats underwent aortic regurgitation and were treated for 6 months with vehicle, olmesartan (an angiotensin II receptor blocker), or hydralazine. At 6 months, albuminuria and glomerular podocyte injury were significantly increased in aortic regurgitation rats. These changes were associated with increased urinary angiotensinogen excretion, kidney angiotensin II and norepinephrine (NE) levels, and enhanced angiotensinogen and angiotensin type 1a receptor gene expression and oxidative stress in renal cortical tissues. Aortic regurgitation rats with renal denervation had decreased albuminuria and glomerular podocyte injury, which were associated with reduced kidney NE, angiotensinogen, angiotensin II, and oxidative stress. Renal denervation combined with olmesartan prevented podocyte injury and albuminuria induced by aortic regurgitation. Conclusions-In this chronic cardiac volume-overload animal model, activation of the sympathetic nervous system augments kidney renin-angiotensin system and oxidative stress, which act as crucial cardiorenal mediators. Renal denervation and olmesartan prevent the onset and progression of renal injury, providing new insight into the treatment of cardiorenal syndrome. (Circulation. 2012;125:1402-1413.)
  • Beneficial direct adipotropic actions of pitavastatin in vitro and their manifestations in obese mice, Yasuhiro Ishihara, Koji Ohmori, Mizuki Mizukawa, Arif Ul. Hasan, Takahisa Noma, Masakazu Kohno, ATHEROSCLEROSIS, 212, (1), 131 - 138,   2010年09月, [査読有り]
    Objective: Prevention of cardiovascular complications in obese patients frequently includes statin administration for coexisting dyslipidemia. Herein, we investigated the impacts of pitavastatin at clinically relevant doses on adipose dysfunction and insulin resistance. Methods: We treated 3T3-L1 preadipocytes with 10-100 ng/ml pitavastatin from initiation of differentiation (Day 0) to Day 8 (differentiation/maturation phase) or from Day 8 to Day 16 (post-maturation phase). Subsequently, we administered pitavastatin (6.2 mg/day/kg) to 7-week-old female KKAy mice for 6 weeks; untreated KKAy mice served as obese controls. Results: Pitavastatin impaired neither lipogenesis nor adiponectin expression during the differentiation/maturation phase. During the post-maturation phase, pitavastatin prevented excessive triglyceride accumulation, which was associated with attenuated glucose transporter-4 expression, and dose-dependently upregulated hormone-sensitive lipase expression. Decrements in the adiponectin/plasminogen activator-1 ratio were also dose-dependently inhibited. In KKAy mice, Coulter counter analyses revealed that pitavastatin treatment significantly decreased (by 16.8%) the frequency of hypertrophic adipocytes (>150 mu m in diameter) in parametrial adipose pads, of which total weight remained unaltered. Correspondingly, plasma adiponectin was significantly higher in pitavastatin-treated KKAy mice than in the untreated KKAy mice (12.5 +/- 3.8 mu g/ml vs. 8.3 +/- 1.5 mu g/ml, p < 0.05). Moreover, the area under the time-glucose curve after intraperitoneal insulin was decreased by 16% in pitavastatin-treated KKAy mice (p < 0.05 vs. untreated controls). Conclusions: Pitavastatin did not impair differentiation/maturation of preadipocytes and prevented their deterioration with hypertrophy after maturation at clinical concentrations in vitro. These effects likely contributed to improved insulin sensitivity, in an obese model, via prevention of adipocyte hypertrophy and adipocytokine dysregulation. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
  • Effects of combined olmesartan and pravastatin on glucose intolerance and cardiovascular remodeling in a metabolic-syndrome model, Mizuki Mizukawa, Koji Ohmori, Ayumi Obayashi, Yasuhiro Ishihara, Junji Yoshida, Takahisa Noma, Kazushi Yukiiri, Hiroaki Kosaka, Masakazu Kohno, HYPERTENSION RESEARCH, 32, (7), 617 - 624,   2009年07月, [査読有り]
    Hypertension and dyslipidemia frequently coexist in patients with progressive insulin resistance and thus constitute metabolic syndrome. We sought to determine the merits of combining an angiotensin II receptor blocker and a 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor in treating this pathological condition. Five-week-old Otsuka Long-Evans Tokushima Fatty rats, a model of metabolic syndrome, were untreated or treated with olmesartan 3 mg kg(-1) per day, pravastatin 30 mg kg(-1) per day or their combination for 25 weeks. Long-Evans Tokushima Otsuka rats served as normal controls. The antihypertensive effect of olmesartan and the lipid-lowering properties of pravastatin were both augmented by the combination. The oral glucose tolerance test revealed that only the combined treatment significantly reduced the area under the time-glucose curve, which was accompanied by augmented adiponectin messenger RNA expression in epididymal adipose tissue. Although the total cardiac endothelial nitric oxide synthetase ( eNOS) content did not significantly differ among the groups, the combined treatment significantly increased the content of dihydrofolate reductase, a key eNOS coupler. Dihydroethidium staining of the aorta showed that the combination most significantly attenuated superoxide production. Moreover, Azan-Mallory staining revealed that the combination most significantly limited the perivascular fibrosis and wall thickening of intramyocardial coronary arteries. In conclusion, the combination of olmesartan and pravastatin augmented adiponectin expression in white adipose tissue and improved glucose tolerance in a rat model of metabolic syndrome, which was associated with more significant ameliorations of cardiovascular redox state and remodeling than those by treatments with either agent alone. Hypertension Research ( 2009) 32, 617-624; doi: 10.1038/hr.2009.63; published online 22 May 2009
  • Contribution of reactive oxygen species to the pathogenesis of left ventricular failure in Dahl salt-sensitive hypertensive rats:3ffects of angiotensin II blockade., Guo P, Nishiyama A, Rahman M, Nagai Y, 野間貴久, Namba T, Ishizawa M, Murakami K, Miyatake A, Ohmori K, Kohno M, J Hypertens., 24,   2006年06月, [査読有り]
  • An antioxidant treatment potentially protects myocardial energy metabolism by regulating uncoupling protein 2 expression in a chronic beta-adrenergic stimulation rat model, M Ishizawa, K Mizushige, T Noma, T Namba, P Guo, K Murakami, T Tsuji, A Miyatake, K Ohmori, M Kohno, LIFE SCIENCES, 78, (25), 2974 - 2982,   2006年05月, [査読有り]
    Excessive beta-adrenergic stimulation causes cardiac toxicity, which also contributes to cardiac oxidative stress. Although uncoupling protein 2 (UCP2), a member of the mitochondrial inner membrane carrier family, can regulate energy efficiency and oxidative stress in mitochondria, little data exist regarding interactions between UCP2 expression and p-adrenergic stimulation induced cardiac oxidative damage. We investigated whether chronic p-adrenergic stimulation induces myocardial energy metabolism abnormality via oxidative stress, including any role of UCP2. We also examined whether 3-methyl-1-phenyl-2-pyrazolin-5-one (MIC-186; edaravone), a potent free radical scavenger, has cardioprotective effects against p-adrenergic stimulation. Male Sprague-Dawley rats received isoproterenol (1.2mg/kg/day) subcutaneously or/and edaravone (30mg/kg/day) orally. Isoproterenol increased the heart/body weight ratio, accompanied by an increase in the level of myocardial thiobarbituric acid reactive substances (TBARS) and a decreased phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. Isoproterenol also markedly increased expressions of UCP2 mRNA (1.74 fold vs. non-isoproterenol) and protein (1.93 fold vs. non-isoproterenol). Edaravone had no apparent effect in hypertrophic responses, but significantly prevented both increases in TBARS and decreases in the PCr/ATP ratio. Edaravone also prevented increases in UCP2 mRNA (0.76 fold vs. isoproterenol) and protein (0.62 fold vs. isoproterenol) expressions against isoproterenol administration. Our results suggest that chronic beta-adrenergic stimulation induces myocardial energy inefficiency via excessive oxidative stress. The antioxidant effect of edaravone has potential to improve energy metabolism abnormalities against beta-adrenergic stimulation. Adequate regulation of UCP2 expression through artificial reduction of oxidative stress may play an important role in protection of the myocardial energy metabolism. (c) 2006 Elsevier Inc. All rights reserved.
  • Treatment of acute myocardial infarction by hepatocyte growth factor gene transfer., Kondo I, Ohmori K, Oshita A, Takeuchi H, Fuke S, Shinomiya K, Noma T, Namba T, Kohno M, J Am Coll Cardiol. 44(3): 644-653, 2004.,   2004年, [査読有り]