論文 - 神津　英至

Anthropometric parameters‐derived estimation of muscle mass predicts all‐cause mortality in heart failure patients

Satoshi Katano, Suguru Honma, Ryohei Nagaoka, Ryo Numazawa, Kotaro Yamano, Yusuke Fujisawa, Katsuhiko Ohori, Hidemichi Kouzu, Akiyoshi Hashimoto, Masaki Katayose, Toshiyuki Yano

ESC Heart Failure ( Wiley )   2022年09月

DOI

AMPデアミナーゼの役割 2型糖尿病合併心不全の新しい治療標的

丹野 雅也, 長南 新太, 小川 俊史, 神津 英至

BIO Clinica ( (株)北隆館 )  37 ( 10 ) 940 - 945  2022年09月

　概要を見る

糖尿病性心筋症は発症早期には左室拡張機能障害を呈し、HFpEFの主要な原因の一つとなる。HFpEFは左室仕事量の増加により顕性化する。筆者らは肥満2型糖尿病モデルラットを用いて、2型糖尿病心筋においてはAMPデアミナーゼの活性が亢進していることを見出した。AMPDは圧負荷下において、adenine nucleotide pool減少に基づくATPの枯渇だけではなく、キサンチン酸化還元酵素による活性酸素種産生の増幅とそれに伴うミトコンドリア呼吸障害およびATP産生抑制を介して左室機能障害を促進する。これらの成績からAMPDは糖尿病性心筋症における新たな治療標的になり得ると考えられる。(著者抄録)

Enhanced nuclear localization of phosphorylated MLKL predicts adverse events in patients with dilated cardiomyopathy

Yugo Fujita, Toshiyuki Yano, Hiromitsu Kanamori, Daigo Nagahara, Atsuko Muranaka, Hidemichi Kouzu, Atsushi Mochizuki, Masayuki Koyama, Nobutaka Nagano, Takefumi Fujito, Ryo Nishikawa, Naoyuki Kamiyama, Marenao Tanaka, Atsushi Kuno, Masaya Tanno, Tetsuji Miura

ESC Heart Failure ( Wiley )   2022年07月

DOI

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, 長岡 凌平, 沼澤 瞭, 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 ( (一社)日本糖尿病学会 )  65 ( Suppl.1 ) S - 172  2022年04月

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, 長岡 凌平, 沼澤 瞭, 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 ( (一社)日本糖尿病学会 )  65 ( Suppl.1 ) S - 172  2022年04月

ZFP36L2 suppresses mTORc1 through a P53-dependent pathway to prevent peri-partum cardiomyopathy in mice.

Hidemichi Kouzu, Yuki Tatekoshi, Hsiang-Chun Chang, Jason S Shapiro, Warren A McGee, Adam De Jesus, Issam Ben-Sahra, Zoltan Arany, Jonathan Leor, Chunlei Chen, Perry J Blackshear, Hossein Ardehali

The Journal of clinical investigation    2022年03月  [国際誌]

　概要を見る

Pregnancy is associated with substantial physiological changes of the heart, and disruptions in these processes can lead to peripartum-cardiomyopathy (PPCM). The molecular processes that cause physiological and pathological changes in the heart during pregnancy are not well characterized. Here, we show that mTORc1 was activated in pregnancy to facilitate cardiac enlargement that was reversed after delivery in mice. mTORc1 activation in pregnancy was negatively regulated by the mRNA-destabilizing-protein ZFP36L2 through its degradation of Mdm2 mRNA and P53 stabilization, leading to increased SESN2 and REDD1 expression. This pathway impeded uncontrolled cardiomyocytes hypertrophy during pregnancy, and mice with cardiac-specific Zfp36l2 deletion developed rapid cardiac dysfunction after delivery, while prenatal treatment of these mice with rapamycin improved post-partum cardiac function. Collectively, these data provide a novel pathway for the regulation of mTORc1 through mRNA stabilization of a P53 ubiquitin ligase. This pathway was critical for normal cardiac growth during pregnancy, and its reduction led to PPCM-like adverse remodeling in mice.

DOI PubMed

Impacts of Proton Pump Inhibitors on Body Composition and Clinical Outcome in Patients with Heart Failure(和訳中)

大堀 克彦, 片野 唆敏, 長岡 凌平, 沼澤 瞭, 神津 英至, 小山 雅之, 永野 伸卓, 藤戸 健史, 西川 諒, 大和田 渉, 矢野 俊之

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  86回   JO09 - 3  2022年03月

サルコペニアを合併する心不全患者の骨密度と性差の関連

沼澤 瞭, 片野 唆敏, 長岡 凌平, 神津 英至, 大堀 克彦, 渡辺 絢子, 藤戸 健史, 西川 諒, 大和田 渉, 永野 伸卓, 小山 雅之, 橋本 暁佳, 矢野 俊之

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  86回   CO2 - 7  2022年03月

高齢心不全における社会的フレイルとその構成要素が予後に及ぼす影響

渡辺 絢子, 片野 唆敏, 柳瀬 理美, 永井 早紀, 米川 葵, 藤田 梨恵, 長岡 凌平, 沼澤 瞭, 大堀 克彦, 神津 英至, 藤戸 健史, 西川 諒, 大和田 渉, 永野 伸卓, 小山 雅之, 橋本 暁佳, 矢野 俊之

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  86回   CO6 - 5  2022年03月

多様なフレイル・サルコペニアと心疾患との関係 サルコペニア合併心不全における骨粗鬆症の併存率ならびに生活機能への影響

片野 唆敏, 長岡 凌平, 矢野 俊之, 沼澤 瞭, 本間 傑, 大堀 克彦, 神津 英至, 渡辺 絢子, 藤戸 健史, 西川 諒, 大和田 渉, 永野 伸卓, 橋本 暁佳, 片寄 正樹, 土橋 和文

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  86回   CS3 - 5  2022年03月

Plasma 3-methylhistidine Predicts the Impact of Renin-angiotensin System Inhibition on Skeletal Muscle Preservation in Heart Failure Patients(和訳中)

神津 英至, 片野 唆敏, 大堀 克彦, 長岡 凌平, 沼澤 瞭, 小山 雅之, 永野 伸卓, 藤戸 健史, 大和田 渉, 西川 諒, 矢野 俊之

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  86回   PJ22 - 6  2022年03月

サルコペニアを合併する心不全患者の骨密度と性差の関連

沼澤 瞭, 片野 唆敏, 長岡 凌平, 神津 英至, 大堀 克彦, 渡辺 絢子, 藤戸 健史, 西川 諒, 大和田 渉, 永野 伸卓, 小山 雅之, 橋本 暁佳, 矢野 俊之

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  86回   CO2 - 7  2022年03月

高齢心不全における社会的フレイルとその構成要素が予後に及ぼす影響

渡辺 絢子, 片野 唆敏, 柳瀬 理美, 永井 早紀, 米川 葵, 藤田 梨恵, 長岡 凌平, 沼澤 瞭, 大堀 克彦, 神津 英至, 藤戸 健史, 西川 諒, 大和田 渉, 永野 伸卓, 小山 雅之, 橋本 暁佳, 矢野 俊之

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  86回   CO6 - 5  2022年03月

心不全患者におけるプロトンポンプ阻害薬の体組成および臨床転帰への影響(Impacts of Proton Pump Inhibitors on Body Composition and Clinical Outcome in Patients with Heart Failure)

大堀 克彦, 片野 唆敏, 長岡 凌平, 沼澤 瞭, 神津 英至, 小山 雅之, 永野 伸卓, 藤戸 健史, 西川 諒, 大和田 渉, 矢野 俊之

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  86回   JO09 - 3  2022年03月

血漿中3-メチルヒスチジンを用いたレニン-アンジオテンシン系阻害剤が心不全患者の骨格筋に及ぼす影響の予測(Plasma 3-methylhistidine Predicts the Impact of Renin-angiotensin System Inhibition on Skeletal Muscle Preservation in Heart Failure Patients)

神津 英至, 片野 唆敏, 大堀 克彦, 長岡 凌平, 沼澤 瞭, 小山 雅之, 永野 伸卓, 藤戸 健史, 大和田 渉, 西川 諒, 矢野 俊之

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  86回   PJ22 - 6  2022年03月

多様なフレイル・サルコペニアと心疾患との関係 サルコペニア合併心不全における骨粗鬆症の併存率ならびに生活機能への影響

片野 唆敏, 長岡 凌平, 矢野 俊之, 沼澤 瞭, 本間 傑, 大堀 克彦, 神津 英至, 渡辺 絢子, 藤戸 健史, 西川 諒, 大和田 渉, 永野 伸卓, 橋本 暁佳, 片寄 正樹, 土橋 和文

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  86回   CS3 - 5  2022年03月

Utility of a Score for Predicting Glomerular Filtration Rate Overestimation in Patients with Cardiovascular and Renal Diseases and Their Risk Factors

Tomoyuki Ishigo, Toshiyuki Yano, Satoshi Katano, Ryo Takada, Tomohiro Aigami, Keita Nakano, Fuki Kondo, Hidemichi Kouzu, Katsuhiko Ohori, Hiromasa Nakata, Masatoshi Nonoyama, Manabu Kitagawa, Tomoko Kimyo, Masahide Fukudo, Tetsuji Miura

Internal Medicine ( Japanese Society of Internal Medicine )  61 ( 2 ) 167 - 175  2022年01月

DOI

Early Detection of Cardiac Amyloidosis in Transthyretin Mutation Carriers: Case Series and Review of the Literature(和訳中)

Nagano Nobutaka, Muranaka Atsuko, Nishikawa Ryo, Ohwada Wataru, Kouzu Hidemichi, Kamiyama Naoyuki, Fujito Takefumi, Mochizuki Atsushi, Nagahara Daigo, Nakanishi Mitsuhiro, Ohkubo Yukiko, Hisahara Shin, Nakao Satoshi, Katoh Nagaaki, Ishikawa Aki, Sakurai Akihiro, Yano Toshiyuki

International Heart Journal ( (一社)インターナショナルハートジャーナル刊行会 )  63 ( 1 ) 168 - 175  2022年01月

Barthel Index Score Predicts Mortality in Elderly Heart Failure - A Goal of Comprehensive Cardiac Rehabilitation.

Satoshi Katano, Toshiyuki Yano, Katsuhiko Ohori, Hidemichi Kouzu, Ryohei Nagaoka, Suguru Honma, Kanako Shimomura, Takuya Inoue, Yuhei Takamura, Tomoyuki Ishigo, Ayako Watanabe, Masayuki Koyama, Nobutaka Nagano, Takefumi Fujito, Ryo Nishikawa, Wataru Ohwada, Akiyoshi Hashimoto, Masaki Katayose, Sumio Ishiai, Tetsuji Miura

Circulation journal : official journal of the Japanese Circulation Society ( (一社)日本循環器学会 )  86 ( 1 ) 70 - 78  2021年12月  [国内誌]

　概要を見る

BACKGROUND: A strategy to predict mortality in elderly heart failure (HF) patients has not been established.Methods and Results:We retrospectively enrolled 413 HF patients aged ≥65 years (mean age 78 years) who had received comprehensive cardiac rehabilitation (CR) during hospitalization. Basic activities of daily life were assessed before discharge using the Barthel index (BI). Of 413 HF patients, 116 (28%) died during a median follow-up period of 1.90 years (interquartile range 1.20-3.23 years). An adjusted dose-dependent association analysis showed that the hazard ratio (HR) of mortality increased in an almost linear manner as the BI score decreased, and that a BI score of 85 corresponded to an HR of 1.0. Kaplan-Meier survival curves showed that the survival rate was lower for patients with a low BI (<85) than for those with a high BI (≥85; 65% vs. 74%, respectively; P=0.007). In multivariate Cox regression analyses, low BI was independently associated with higher mortality after adjusting for predictors, including B-type natriuretic peptide. Inclusion of the BI into the adjusted model improved the accuracy of the prediction of mortality. CONCLUSIONS: A BI score <85 at the time of discharge is associated with increased mortality independent of known prognostic markers, and achieving functional status with a BI score ≥85 by comprehensive CR during hospitalization may contribute to favorable outcomes in elderly HF patients.

DOI PubMed

Plasma amino acid profiling improves predictive accuracy of adverse events in patients with heart failure.

Hidemichi Kouzu, Satoshi Katano, Toshiyuki Yano, Katsuhiko Ohori, Ryohei Nagaoka, Takuya Inoue, Yuhei Takamura, Tomoyuki Ishigo, Ayako Watanabe, Masayuki Koyama, Nobutaka Nagano, Takefumi Fujito, Ryo Nishikawa, Wataru Ohwada, Tetsuji Miura

ESC heart failure   8 ( 6 ) 5045 - 5056  2021年12月  [国際誌]

　概要を見る

AIMS: The clinical outcome of heart failure (HF) is complicated by the presence of multiple comorbidities including malnutrition and cachexia, and prediction of the outcome is still difficult in each patient. Metabolomics including amino acid profiling enables detection of alterations in whole body metabolism. The aim of this study was to determine whether plasma amino acid profiling improves prediction of clinical outcomes in patients with HF. METHODS AND RESULTS: We retrospectively examined 301 HF patients (70 ± 15 years old; 59% male). Blood samples for measurements of amino acid concentrations were collected in a fasting state after stabilization of HF. Plasma amino acid concentrations were measured using ultraperformance liquid chromatography. Clinical endpoint of this study was adverse event defined as all-cause death and unscheduled readmission due to worsening HF or lethal arrhythmia. During a mean follow-up period of 380 ± 214 days, 40 patients (13%) had adverse events. Results of analyses of variable importance in projection score, a measure of a variable's importance in partial least squares-discriminant analysis (PLS-DA) showed that the top five amino acids being associated with adverse events were 3-methylhistidine (3-Me-His), β-alanine, valine, hydroxyproline, and tryptophan. Multivariate Cox-proportional hazard analyses indicated that a high 3-Me-His concentration and low β-alanine and valine concentrations were independently associated with adverse events. When HF patients were divided according to the cut-off values of amino acids calculated from receiver operating characteristic curves, Kaplan-Meier survival curves showed that event-free survival rates were lower in HF patients with high 3-Me-His than in HF patients with low 3-Me-His (68% vs. 91%, P < 0.01). In a subgroup with high 3-Me-His, HF patients with low β-alanine and those with low valine had significantly lower event-free survival rates than did HF patients with high β-alanine and those with high valine, respectively. On the other hand, Kaplan-Meier curves of event-free survival rates did not differ between HF patients with and those without low β-alanine and low valine in subgroups of patients with low 3-Me-His. Inclusion of both high 3-Me-His and low β-alanine or low valine into the adjustment model including N-terminal pro-brain natriuretic peptide improved the accuracy of prediction of adverse events after discharge. 3-Me-His concentration was associated with muscle mass and nutritional status. CONCLUSIONS: Simple measurement of 3-Me-His with either β-alanine or valine improved the predictive ability for adverse events, indicating the utility of plasma amino acid profiling in risk stratification of hospitalized HF patients.

DOI PubMed