Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University School of Medicine   Department of Cardiovascular, Renal and Metabolic Medicine  

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Associations between in‐hospital daily protein intake and adverse clinical outcomes in older patients with heart failure

  Satoshi Katano, Toshiyuki Yano, Kotaro Yamano, Ryo Numazawa, Ryohei Nagaoka, Suguru Honma, Yusuke Fujisawa, Katsuhiko Ohori, Hidemichi Kouzu, Hayato Kunihara, Hiroya Fujisaki, Masaki Katayose, Akiyoshi Hashimoto, Masato Furuhashi

  ESC Heart Failure ( Wiley )   2024.05

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  Abstract Aims The adverse effects of low daily protein intake (DPI) on clinical outcomes in patients with heart failure (HF) are known; however, an optimal DPI to predict event adverse outcomes remains undetermined. Moreover, whether protein restriction therapy for chronic kidney disease is applicable in patients with HF and renal dysfunction remains unclear. Methods and results In this single‐centre, ambispective cohort study, we included 405 patients with HF aged ≥65 years (mean age, 78.6 ± 7.5 years; 50% women). DPI was estimated from consumption over three consecutive days before discharge and normalized relative to the ideal body weight [IBW, 22 kg/m² × height (m)²]. The primary outcome was a composite of all‐cause mortality and HF‐related readmission within the 2 year post‐discharge period. Results During an average follow‐up period of 1.49 ± 0.74 years, 100 patients experienced composite events. Kaplan–Meier survival curves revealed a significantly lower composite event‐free rate in patients within the lowest quartile of DPI than in the upper quartiles (log‐rank test, P = 0.02). A multivariate Cox proportional hazards analysis after adjusting for established prognostic markers and non‐proteogenic energy intake revealed that patients in the lowest DPI quartile faced a two‐fold higher risk of composite events than those in the highest quartile [hazard ratio (HR), 2.03; 95% confidence interval (CI), 1.08–3.82; P = 0.03]. The composite event risk linearly increased as DPI decreased (P for nonlinearity = 0.90), with each standard deviation (0.26 g/kg IBW/day) decrease in DPI associated with a 32% increase in composite event risk (HR, 1.32; 95% CI, 1.10–1.71; P = 0.04). There was significant heterogeneity in the effect of DPI, with the possible disadvantage of lower DPI in patients with HF with cystatin C‐based estimated glomerular filtration rate <30 mL/min/1.73 m². The cutoff value of DPI for predicting the occurrence of composite events calculated from the Youden index was 1.12 g/kg IBW/day. Incorporating a DPI < 1.12 g/kg IBW/day into the baseline model significantly improved the prediction of post‐discharge composite events (continuous net reclassification improvement, 0.294; 95% CI, 0.072–0.516; P = 0.01). Conclusions Lower DPI during hospitalization is associated with an increased risk of mortality and HF readmission independent of non‐proteogenic energy intake, and the possible optimal DPI for predicting adverse clinical outcomes is >1.12 g/kg IBW/day in older patients with HF. Caution is warranted when protein restriction therapy is administered to older patients with HF and renal dysfunction.

  DOI

• Which came first: Sarcopenia or weight loss?

  Katsuhiko Ohori, Toshiyuki Yano, Satoshi Katano, Ryohei Nagaoka, Ryo Numazawa, Kotaro Yamano, Yusuke Fujisawa, Hidemichi Kouzu, Nobutaka Nagano, Takefumi Fujito, Ryo Nishikawa, Wataru Ohwada, Masato Furuhashi

  Geriatrics &amp; Gerontology International ( Wiley )   2024.04

  DOI

• Downregulation of Mitochondrial Fusion Protein Expression Affords Protection from Canonical Necroptosis in H9c2 Cardiomyoblasts

  Yuki Toda, Sang-Bing Ong, Toshiyuki Yano, Atsushi Kuno, Hidemichi Kouzu, Tatsuya Sato, Wataru Ohwada, Yuki Tatekoshi, Toshifumi Ogawa, Masaki Shimizu, Masaya Tanno, Masato Furuhashi

  International Journal of Molecular Sciences ( MDPI AG )  25 ( 5 ) 2905 - 2905  2024.03

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  Necroptosis, a form of necrosis, and alterations in mitochondrial dynamics, a coordinated process of mitochondrial fission and fusion, have been implicated in the pathogenesis of cardiovascular diseases. This study aimed to determine the role of mitochondrial morphology in canonical necroptosis induced by a combination of TNFα and zVAD (TNF/zVAD) in H9c2 cells, rat cardiomyoblasts. Time-course analyses of mitochondrial morphology showed that mitochondria were initially shortened after the addition of TNF/zVAD and then their length was restored, and the proportion of cells with elongated mitochondria at 12 h was larger in TNF/zVAD-treated cells than in non-treated cells (16.3 ± 0.9% vs. 8.0 ± 1.2%). The knockdown of dynamin-related protein 1 (Drp1) and fission 1, fission promoters, and treatment with Mdivi-1, a Drp-1 inhibitor, had no effect on TNF/zVAD-induced necroptosis. In contrast, TNF/zVAD-induced necroptosis was attenuated by the knockdown of mitofusin 1/2 (Mfn1/2) and optic atrophy-1 (Opa1), proteins that are indispensable for mitochondrial fusion, and the attenuation of necroptosis was not canceled by treatment with Mdivi-1. The expression of TGFβ-activated kinase (TAK1), a negative regulator of RIP1 activity, was upregulated and the TNF/zVAD-induced RIP1-Ser166 phosphorylation, an index of RIP1 activity, was mitigated by the knockdown of Mfn1/2 or Opa1. Pharmacological TAK1 inhibition attenuated the protection afforded by Mfn1/2 and Opa1 knockdown. In conclusion, the inhibition of mitochondrial fusion increases TAK1 expression, leading to the attenuation of canonical necroptosis through the suppression of RIP1 activity.

  DOI

• Role of AMP deaminase in diabetic cardiomyopathy

  Tetsuji Miura, Hidemichi Kouzu, Masaya Tanno, Yuki Tatekoshi, Atsushi Kuno

  Molecular and Cellular Biochemistry ( Springer Science and Business Media LLC )   2024.02

  DOI

• Coexistence of sarcopenia and self‐reported weight loss is a powerful predictor of mortality in older patients with heart failure

  Katsuhiko Ohori, Toshiyuki Yano, Satoshi Katano, Ryohei Nagaoka, Ryo Numazawa, Kotaro Yamano, Yusuke Fujisawa, Hidemichi Kouzu, Nobutaka Nagano, Takefumi Fujito, Ryo Nishikawa, Wataru Ohwada, Masato Furuhashi

  Geriatrics &amp; Gerontology International ( Wiley )   2023.12

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  Aim We examined whether the addition of self‐reported weight loss improves the accuracy of prediction of mortality caused by sarcopenia in heart failure (HF) patients. Methods We enrolled 477 HF patients (mean age 77 years) who received combined assessment of sarcopenia and self‐reported weight loss. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia. If the patients answered “yes” to the question “have you lost 2 kg or more in the past 6 months?”, they were diagnosed as having self‐reported weight loss. Results Sarcopenia and self‐reported weight loss coexisted in 32% of patients. During a median follow‐up period of 763 days, 65 patients (15%) died. Kaplan–Meier curves showed a significantly higher rate of mortality in HF patients with both sarcopenia and self‐reported weight loss than in HF patients with sarcopenia alone. Multivariate Cox proportional hazards analysis showed that the coexistence of sarcopenia and self‐reported weight loss is an independent predictor of mortality in HF patients. Inclusion of the coexistence of sarcopenia and self‐reported weight loss in the baseline model consisting of established prognostic markers significantly improved both the net reclassification index and the integrated discrimination index. Conclusions The coexistence of sarcopenia and self‐reported weight loss is a powerful predictor of mortality in HF patients. Geriatr Gerontol Int 2023; ••: ••–••.

  DOI

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 脳梗塞発症を契機に診断されたLoffler心内膜心筋炎を伴う好酸球性多発血管炎性肉芽腫症の1例—A case of eosinophilic granulomatosis with polyangiitis complicated with Loffler's endocarditis diagnosed by the onset of cerebral infarction

  大和田 渉, 矢野 俊之, 赤澤 史子, 神津 英至, 續 太郎, 宮森 大輔, 西川 諒, 永野 伸卓, 小山 雅之, 村中 敦子, 丹野 雅也

  日本内科学会雑誌   111 ( 8 ) 1580 - 1587  2022.08

• Case Report; A case of eosinophilic granulomatosis with polyangiitis complicated with Loeffler’s endocarditis diagnosed by the onset of cerebral infarction.

  大和田渉, 矢野俊之, 赤澤史子, 神津英至, 續太郎, 宮森大輔, 西川諒, 永野伸卓, 小山雅之, 村中敦子, 丹野雅也

  日本内科学会雑誌   111 ( 8 )  2022

  J-GLOBAL

• 糖尿病合併心不全における血漿分枝鎖アミノ酸の規定因子と予後予測能の検討

  神津英至, 片野唆敏, 大堀克彦, 大堀克彦, 長岡凌平, 沼澤瞭, 小山雅之, 小山雅之, 永野伸卓, 藤戸健史, 大和田渉, 佐藤達也, 矢野俊之

  糖尿病(Web)   65 ( Suppl )  2022

  J-GLOBAL

• 慢性心不全患者におけるShrunken Pore Syndromeと心血管イベントの関連性

  石郷 友之, 片野 唆敏, 矢野 俊之, 神津 英至, 大堀 克彦, 小山 雅之, 永野 伸卓, 藤戸 健史, 渡辺 絢子, 中野 敬太, 相神 智宏, 野々山 雅俊, 北川 学, 木明 智子, 藤居 賢, 戸田 貴大, 福士 将秀

  日本腎臓病薬物療法学会誌 ( 日本腎臓病薬物療法学会 )  10 ( 特別号 ) S152 - S152  2021.10

  J-GLOBAL

• プロトンポンプ阻害薬が心不全患者の骨格筋量に与える影響

  大堀 克彦, 矢野 俊之, 片野 唆敏, 長岡 凌平, 神津 英至, 永野 伸卓, 藤戸 健史, 西川 諒, 大和田 渉, 土橋 和文

  日本心臓病学会学術集会抄録 ( (一社)日本心臓病学会 )  69回   O - 104  2021.09

  J-GLOBAL

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• アミノ酸ー核酸代謝連関の制御による心不全の新規治療開発

  基盤研究(C)

  Project Year :

  2020.04

  -

  2023.03

   

  神津 英至, 久野 篤史, 矢野 俊之

  　View Summary

  ラット心筋におけるプロテオミクス解析において、AMPD3と分枝鎖アミノ酸(BCAA)の代謝律速酵素である分枝鎖α-ケト酸脱水素酵素(BCKDH)が直接結合していることを同定し、BCAA代謝の制御にAMPD3が関与していることが示唆された。さらに細胞分画実験において、この結合が細胞質及び小胞体分画で見られることを同定し、心筋においてBCAAがミトコンドリア外でも代謝されている可能性を見出した。新生ラット初代心筋細胞(NRCM)において、BCKDHサブユニットのノックダウンによって脂肪滴合成能障害がみられ、BCAA代謝が脂肪酸代謝に寄与してることを同定した。2型糖尿病モデルラット(OLETF)心筋において、BCAAの蓄積及びBCKDH-AMPD3結合比の低下がみられ、糖尿病心筋におけるBCAA代謝障害にAMPD3が関与している可能性が示唆された。さらに、OLETFの心筋メタボローム解析にて、SGLT2阻害薬によって最も増加傾向を示す代謝物がBCAAを始めとするアミノ酸であることを同定し、SGLT2阻害薬の心保護効果の機序としてアミノ酸代謝修飾の関与を同定した。 また、心不全症例において、血中アミノ酸プロファイリングが既存の危険因子と独立して予後を予測することを見出した。

• Molecular mechanisms of left ventricular diastolic dysfunction in the type 2 diabetic heart

  Grant-in-Aid for Young Scientists (B)

  Project Year :

  2013.04

  -

  2015.03

   

  KOUZU Hidemichi

  　View Summary

  The aim of this study was to examine mechanisms by which type 2 diabetes (T2DM) augments ventricular diastolic stiffness in response to pressure overloading. We found that AMP deaminse activity was increased in T2DM hearts, resulting in excessive degradation of adenine nucleotides and ATP depletion during pressure overloading. ATP level was negatively correlated with tau of LV pressure and LVEDP. These diastolic properties were observed before development of extracellular matrix or titin remodeling.