論文 - 丹野　雅也

Toll様受容体の活性化により2型糖尿病における心筋梗塞後のAKIに対する腎臓の感受性が増大する(Increased Renal Susceptibility to AKI after Myocardial Infarction in Type 2 Diabetes is Mediated by Augmented Activation of Toll-like Receptors)

大野 紘平, 久野 篤史, 三木 隆幸, 丹野 雅也, 矢野 俊之, 大和田 渉, 木村 幸滋, 安部 功記, 中田 圭, 舘越 勇輝, 三浦 哲嗣

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  81回   PJ - 594  2017年03月

多発性脳梗塞にて発症し、診断と治療効果の指標にPET-CTが有用であったLoeffler心内膜心筋炎の1例

大岩 修太郎, 茂庭 仁人, 能登 貴弘, 瀬野 結, 永野 伸卓, 神津 英至, 村中 敦子, 矢野 俊之, 丹野 雅也, 三浦 哲嗣

心臓 ( (公財)日本心臓財団 )  49 ( 3 ) 253 - 259  2017年03月

　概要を見る

症例は70歳代、男性。2012年近医で好酸球増多を認めたが精査は行われなかった。2015年7月に複視を契機に多発性脳梗塞と診断され、心原性脳塞栓症の疑いで当科紹介入院となった。血液検査にてCRP高値(6.76mg/dL)に加え好酸球数(6,615/μL)と、好酸球脱顆粒の指標である好酸球性カチオン性蛋白(41.7μg/L)の著明な上昇を認めた。右室心内膜下心筋生検にて有意な所見は認めなかったが、PET-CTにて左室心尖部心内膜に異常集積を認めたため、Loeffler心内膜心筋炎による左室内血栓からの多発性脳梗塞と考え、プレドニゾロンおよび抗凝固療法を開始した。その後速やかにCRPと好酸球数は正常化し、塞栓症の再発は認めず、慢性期のPET-CTでは左室心尖部心内膜下の異常集積は消失していた。本症例では炎症病変が左室心尖部であったため右室中隔から採取した心筋生検に異常を認めなかったものと考えられた。動脈塞栓症に好酸球増加症を合併した場合、Loeffler心内膜心筋炎を念頭に早期にPET-CTを含めた精査、治療介入を行うことが重要である。(著者抄録)

Distinct risk factors of atrial fibrillation in patients with and without coronary artery disease: A cross-sectional analysis of the BOREAS-CAG Registry data

Naoto Murakami, Masaya Tanno, Nobuaki Kokubu, Junichi Nishida, Nobutaka Nagano, Hirofumi Ohnishi, Hiroshi Akasaka, Takayuki Miki, Kazufumi Tsuchihashi, Tetsuji Miura

Open Heart ( BMJ Publishing Group )  4 ( 1 ) e000573  2017年  [査読有り]

　概要を見る

Objective: Although risk factors of atrial fibrillation (AF) in the general population have been characterised, their impacts on patients with specific diseases are unclear. Our aim was to determine whether risk factors of AF are different in patients with and those without coronary artery disease (CAD). Methods: We enrolled 1871 consecutive patients who underwent coronary angiography for evaluation of symptoms suggestive of CAD in the BOREAS-CAG Registry between August 2014 and January 2015. After exclusion of patients with valvular heart disease or a history of PCI/cardiac surgery, 1150 patients contributed to multivariate logistic regression analysis to identify risk factors of AF. We also retrieved data for 361 consecutive patients with CAD admitted to Sapporo Medical University Hospital between April 2013 and July 2014 and analysed data for 166 patients using the same inclusion and exclusion criteria as those in the BOREAS-CAG Registry. Results: Unexpectedly, CAD was independently associated with the absence of AF. The patients were then divided into a non-CAD group (n=576) and a CAD group (n=574) for further analysis. The brain natriuretic peptide level showed a strong association with AF regardless of the presence or absence of CAD. In the non-CAD group, lack of statin use was independently associated with AF, whereas high serum uric acid level was an independent explanatory variable of AF in the CAD group. The association of AF with uric acid was confirmed in a separate group of patients (n=166) enrolled in the CAD cohort in Sapporo Medical University Hospital. Conclusions: Major risk factors of AF are different in patients with CAD and those without CAD. Patients with CAD are more likely to develop AF when the serum uric acid level is high, whereas no statin administration predicts development of AF in patients without CAD.

DOI PubMed

Chronic Treatment With an Erythropoietin Receptor Ligand Prevents Chronic Kidney Disease-Induced Enlargement of Myocardial Infarct Size.

Nishizawa K, Yano T, Tanno M, Miki T, Kuno A, Tobisawa T, Ogasawara M, Muratsubaki S, Ohno K, Ishikawa S, Miura T

Hypertension (Dallas, Tex. : 1979)   68 ( 3 ) 697 - 706  2016年09月  [査読有り]

DOI PubMed

糖尿病が腎虚血再灌流障害に及ぼす影響 オートファジーとの関連

村椿 真悟, 久野 篤史, 大野 紘平, 丹野 雅也, 矢野 俊之, 水野 雅司, 西沢 慶太郎, 大和田 渉, 舘越 勇輝, 中田 圭, 三木 隆幸, 三浦 哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 )  58 ( 3 ) 276 - 276  2016年05月

睡眠呼吸障害が血糖変動に与える影響の検討

中田 圭, 丹野 雅也, 矢野 俊之, 小笠原 淳, 赤坂 憲, 古橋 眞人, 三木 隆幸, 三浦 哲嗣

糖尿病 ( (一社)日本糖尿病学会 )  59 ( Suppl.1 ) S - 191  2016年04月

RIP1によるp62の隔離はオートファジーの流れを障害し、心筋細胞におけるRIP1依存的ネクロトーシスにつながる(Sequestration of p62 by RIP1 Impairs Autophagic Flux and Leads to RIP1-dependent Necroptosis in Cardiomyocytes)

Ogasawara Makoto, Yano Toshiyuki, Miki Takayuki, Tanno Masaya, Kuno Atsushi, Kouzu Hidemichi, Tobisawa Toshiyuki, Muratsubaki Shingo, Ono Kouhei, Nishizawa Keitaro, Ishikawa Satoko, Miura Tetsuji

Circulation Journal ( (一社)日本循環器学会 )  80 ( Suppl.I ) 2404 - 2404  2016年03月

糖尿病心臓のAMP deaminaseの活性化においては翻訳後修飾ではなくfructose 1,6-diphosphateの枯渇が主要な役割を果たす(Depletion of Fructose 1,6-diphosphate but not Post-translational Modification Plays a Major Role in Activation of AMP Deaminase in Diabetic Hearts)

Tatekoshi Yuki, Kouzu Hidemichi, Tanno Masaya, Kuno Atsushi, Ishikawa Satoko, Yano Toshiyuki, Miki Takayuki, Ogasawara Makoto, Tobisawa Toshiyuki, Ono Kouhei, Muratsubaki Shingo, Nishizawa Keitaro, Miura Tetsuji

Circulation Journal ( (一社)日本循環器学会 )  80 ( Suppl.I ) 1115 - 1115  2016年03月

2型糖尿病初期ではAMI誘発性急性腎障害に対する感受性がTLR介在性メカニズムによって増加する(Susceptibility to AMI-induced Acute Kidney Injury is Increased by a TLR-mediated Mechanism in the Early Stage of Type 2 Diabetes)

Ono Kouhei, Kuno Atsushi, Miki Takayuki, Tanno Masaya, Yano Toshiyuki, Kouzu Hidemichi, Ogasawara Makoto, Tobisawa Toshiyuki, Muratsubaki Shingo, Nishizawa Keitaro, Miura Tetsuji

Circulation Journal ( (一社)日本循環器学会 )  80 ( Suppl.I ) 1352 - 1352  2016年03月

Clinical impact of myocardial mTORC1 activation in nonischemic dilated cardiomyopathy

Toshiyuki Yano, Shinya Shimoshige, Takayuki Miki, Masaya Tanno, Atsushi Mochizuki, Takefumi Fujito, Satoshi Yuda, Atsuko Muranaka, Makoto Ogasawara, Akiyoshi Hashimoto, Kazufumi Tsuchihashi, Tetsuji Miura

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY ( ELSEVIER SCI LTD )  91   6 - 9  2016年02月  [査読有り]

　概要を見る

Background: Activity of mTOR complex 1 (mTORC1) has been shown to be up-regulated in animal models of heart failure. Here, we investigated the change and role of mTORC1 in human nonischemic dilated cardiomyopathy (NICM). Methods: Endomyocardial biopsy specimens were obtained from patients with NICM (n = 52) and from Brugada syndrome patients with normal LVEF as controls (n = 10). The specimens were stained for phospho-ribosomal protein S6 (p-RpsG) and phospho-p70S6K (p-p70S6K), and the area with p-RpsG signal was used as an index of mTORC1 activity. Using median mTORC1 activity, patients were divided into a high mTORC1 activity (H-mTOR) group and a low mTORC1 activity (L-mTOR) group. Results: The ratio of p-Rps6-positive area in biopsy samples was 10-fold larger in patients with NICM than in controls (2.0 +/- 22% vs. 0.2 +/- 0.2%, p < 0.01). p-p70S6K signal level was higher in the H-mTOR group than in the L-mTOR group. The proportion of patients with a family history of cardiomyopathy was higher and the proportion of patients on ACE inhibitors or angiotensin receptor blockers was lower in the H-mTOR group than in the L-mTOR group. The p-Rps6-positive area was correlated with extent of myocardial fibrosis (r = 0.46, p < 0.01). The cardiac event-free survival rate during a 5-year follow-up period tended to be lower in the H-mTOR group than in the L-mTOR group (52.9% vs. 81.6%, P = 0.10). Conclusion: Aberrant activation of mTORC1 in cardiomyocytes was associated with myocardial fibrosis and a trend for worse prognosis in patients with NICM, indicating that persistently activated mTORC1 contributes to progression of human heart failure. (C) 2015 Elsevier Ltd. All rights reserved.

DOI

Inhibition of DPP-4 reduces acute mortality after myocardial infarction with restoration of autophagic response in type 2 diabetic rats.

Murase H, Kuno A, Miki T, Tanno M, Yano T, Kouzu H, Ishikawa S, Tobisawa T, Ogasawara M, Nishizawa K, Miura T

Cardiovascular diabetology   14   103  2015年08月  [査読有り]

DOI PubMed

心筋梗塞による急性腎障害に対する2型糖尿病の影響と死亡率の関連

大野 紘平, 久野 篤史, 村椿 真悟, 村瀬 弘通, 丹野 雅也, 矢野 俊之, 神津 英至, 飛澤 利之, 小笠原 惇, 西澤 慶太郎, 石川 聡子, 田中 希尚, 三木 隆幸, 三浦 哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 )  57 ( 3 ) 569 - 569  2015年04月

早期2型糖尿病腎ではオートファジーが亢進している

村椿 真悟, 久野 篤史, 大野 紘平, 丹野 雅也, 矢野 俊之, 神津 英至, 田中 希尚, 飛澤 利之, 小笠原 惇, 西沢 慶太郎, 石川 聡子, 三木 隆幸, 三浦 哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 )  57 ( 3 ) 569 - 569  2015年04月

慢性腎不全の虚血/再灌流障害への感受性亢進において再灌流中のmTORC2活性化障害は中心的な役割を果たす(Impairment of mTORC2 Activation upon Reperfusion Plays a Pivotal Role in Increased Susceptibility to Ischemia/Reperfusion Injury in Chronic Renal Failure)

Tobisawa Toshiyuki, Yano Toshiyuki, Miki Takayuki, Tanno Masaya, Kuno Atsushi, Kouzu Hidemichi, Ogasawara Makoto, Muratsubaki Shingo, Nishizawa Keutarou, Sugawara Hirohito, Ishikawa Satoko, Yoshida Hideaki, Miura Tetsuji

Circulation Journal ( (一社)日本循環器学会 )  79 ( Suppl.I ) 2071 - 2071  2015年03月

Excessive degradation of adenine nucleotides by up-regulated AMP deaminase underlies afterload-induced diastolic dysfunction in the type 2 diabetic heart.

Kouzu H, Miki T, Tanno M, Kuno A, Yano T, Itoh T, Sato T, Sunaga D, Murase H, Tobisawa T, Ogasawara M, Ishikawa S, Miura T

Journal of molecular and cellular cardiology   80   136 - 145  2015年03月  [査読有り]

DOI PubMed

The effects of resveratrol and SIRT1 activation on dystrophic cardiomyopathy

Atsushi Kuno, Masaya Tanno, Yoshiyuki Horio

RESVERATROL AND HEALTH ( BLACKWELL SCIENCE PUBL )  1348   46 - 54  2015年  [査読有り]

　概要を見る

The muscular dystrophies, which cause progressive weakening of the skeletal muscles, are frequently associated with cardiomyopathy. In fact, the leading cause of mortality in patients with Duchenne muscular dystrophy, the most common and most severe type of muscular dystrophy, is heart failure due to cardiomyopathy. Therefore, more effective methods for treating cardiomyopathy are expected to improve long-term outcomes for patients with Duchenne muscular dystrophy. Our recent preclinical data show that treatment with the SIRT1 activator resveratrol is beneficial for dystrophic cardiomyopathy. We examined the effects of resveratrol treatment in two different models of muscular dystrophy: dystrophin-deficient mdx mice and delta-sarcoglycan-deficient TO-2 hamsters. In both models, resveratrol suppressed cardiac hypertrophy, preserved cardiac function, and reduced tissue fibrosis in the diseased heart. Importantly, resveratrol significantly improved survival in TO-2 hamsters. Resveratrol also attenuated skeletal muscle pathology in mdx mice. These promising results indicate resveratrol's potential for clinical translation to treat cardiomyopathy in patients with muscular dystrophies.

DOI

Translocation of Glycogen Synthase Kinase-3 beta (GSK-3 beta), a Trigger of Permeability Transition, Is Kinase Activity-dependent and Mediated by Interaction with Voltage-dependent Anion Channel 2 (VDAC2)

Tanno Masaya, Kuno Atsushi, Ishikawa Satoko, Miki Takayuki, Kouzu Hidemichi, Yano Toshiyuki, Murase Hiromichi, Tobisawa Toshiyuki, Ogasawara Makoto, Horio Yoshiyuki, Miura Tetsuji

JOURNAL OF BIOLOGICAL CHEMISTRY   289 ( 42 ) 29285 - 29296  2014年10月  [査読有り]

DOI

Does glycemic control reverse dispersion of ventricular repolarization in type 2 diabetes?

Takayuki Miki, Toshiyuki Tobisawa, Tatsuya Sato, Masaya Tanno, Toshiyuki Yano, Hiroshi Akasaka, Atsushi Kuno, Makoto Ogasawara, Hiromichi Murase, Shigeyuki Saitoh, Tetsuji Miura

CARDIOVASCULAR DIABETOLOGY ( BIOMED CENTRAL LTD )  13   125  2014年08月  [査読有り]

　概要を見る

Background: Abnormal ventricular repolarization is a predictor of cardiovascular mortality. In this study, we tested the hypothesis that glycemic control reverses abnormal ventricular repolarization in patients with type 2 diabetes. Methods: We analyzed longitudinal changes in repolarization indices of electrocardiograms in retrospectively enrolled 44 patients with type 2 diabetes and 44 age-matched healthy subjects. Results: In the diabetic group, BMI was greater, levels of HbA1c (10.0 +/- 1.6 vs. 5.6 +/- 0.3%) and triglyceride were higher and level of HDL cholesterol was lower than those in the control group. Although mean QTc intervals were similar (413.6 +/- 18.5 vs. 408.3 +/- 22.7 ms), QT dispersion (41.8 +/- 15.4 vs. 28.7 +/- 7.7 ms) and Tpeak-Tend in lead V5 (83.6 +/- 13.6 vs. 71.3 +/- 10.3 ms) were significantly longer in the diabetic group than in the control group, indicating increased heterogeneity of ventricular repolarization in type 2 diabetes. During follow-up of 36 patients in the diabetic group for 787 +/- 301 days, HbA1c level decreased to 7.3 +/- 1.6%, while BMI did not significantly change. In contrast to HbA1c, QT dispersion (45.8 +/- 15.0 ms) and Tpeak-Tend in lead V5 (83.6 +/- 10.6 ms) were not significantly reduced during the follow-up period. There was no correlation between the change in HbA1c and the change in QT dispersion or Tpeak-Tend. Conclusions: Increased heterogeneity of ventricular repolarization in type 2 diabetic patients was not reduced during the relatively short follow-up period despite significantly improved glycemic control.

DOI PubMed

Type 2 diabetes induces subendocardium-predominant reduction in transient outward K+ current with downregulation of Kv4.2 and KChIP2.

Sato T, Kobayashi T, Kuno A, Miki T, Tanno M, Kouzu H, Itoh T, Ishikawa S, Kojima T, Miura T, Tohse N

American journal of physiology. Heart and circulatory physiology   306 ( 7 ) H1054 - 65  2014年04月  [査読有り]

DOI PubMed

ミトコンドリアKATPチャンネル活性化による酸化ストレス後のmPTP再閉鎖促進は残存ROS産生の抑制により達成される(Acceleration of mPTP Re-closure after Oxidant Stress by Mitochondrial KATP Channel Activation is Achieved by Suppression of Residual ROS Production)

Ogasawara Makoto, Tanno Masaya, Kuno Atsushi, Ishikawa Satoko, Murase Hiromichi, Tobisawa Toshiyuki, Kouzu Hidemichi, Yano Toshiyuki, Miki Takayuki, Miura Tetsuji

Circulation Journal ( (一社)日本循環器学会 )  78 ( Suppl.I ) 323 - 324  2014年03月