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医学部 医学科 社会医学講座データマネジメント分野 |
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Pyruvate kinase M2 and Serine Dehydratase are Upregulated in the Macrophages of Human Aortic Atherosclerotic Lesions via Inflammatory Stimuli. 査読あり
Nakamura E, Nishimura M, Maekawa K, Gi T, Oguri N, Aman M, Moriguchi-Goto S, Nakai M, Furukawa K, Yamashita A
Journal of atherosclerosis and thrombosis advpub ( 0 ) 2026年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本動脈硬化学会
<b>Aim</b>: An altered vascular metabolism is closely linked to the cellular function in atherosclerotic lesions. The plasma pyruvate levels have been associated with aortic aneurysm progression in clinical studies. Pyruvate kinase M2 (PKM2) and serine dehydratase (SDS) catalyze the final steps of pyruvate production. While PKM2’s role has been examined in experimental atherosclerosis or aneurysms, the involvement of SDS in atherosclerosis and the expression of PKM2 and SDS in human aortic lesions remain unknown.<b>Methods</b>: Human aortic samples from vascular surgery were classified as early (<i>n</i> = 10), advanced (<i>n</i> = 9), or aneurysmal (<i>n</i> = 15) lesions. PKM2 and SDS expression were analyzed using immunohistochemistry.<b>Results</b>: Immunopositive areas for these enzymes were larger in advanced and aneurysmal lesions than in early lesions and were predominantly expressed in macrophages. PKM2 was also detected in some smooth muscle cells and lymphocytes. In cultured human monocyte-derived macrophages, stimulation with tumor necrosis factor-α and interferon-γ increased the PKM2 and SDS expression levels. PKM2 silencing enhanced monocyte chemoattractant protein-1, interleukin-6, and SDS expression, and reduced transforming growth factor-β expression. SDS silencing significantly reduced the reactive oxygen species levels.<b>Conclusions</b>: The PKM2 and SDS expression levels increase in advanced human aortic atherosclerotic lesions and they are predominantly expressed in macrophages. The inflammatory microenvironment in atherosclerotic lesions upregulates the PKM2 and SDS expression in human macrophages. PKM2 may act as a negative regulator of vascular inflammation, and SDS may affect oxidative stress in inflammatory-stimulated macrophages.
DOI： 10.5551/jat.66119
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Iwai T, Takagi K, Kitai T, Asaumi Y, Sumita Y, Iwanaga Y, Nakai M, Noguchi T, Miyamoto Y, Nochioka K, Nakayama M, Akashi N, Matoba T, Kohro T, Oba Y, Kabutoya T, Imai Y, Kario K, Kiyosue A, Mizuno Y, Ishii M, Nakamura T, Tsujita K, Matoba Y, Sato H, Fujita H, Nagai R, CLIDAS research group
International journal of cardiology. Heart & vasculature 64 101929 - 101929 2026年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Ijc Heart and Vasculature
Background: Coronary artery disease (CAD) and aortic valve stenosis (AS) often coexist, with AS exacerbating myocardial ischemia and affecting prognosis. Aims: To investigate the prognostic impact of AS stratified by peak aortic jet velocity (AV-Vel) in patients undergoing PCI. Methods and results: We conducted retrospective multicenter observational study involving patients who underwent percutaneous coronary intervention (PCI) between April 2013 and March 2019. The patients were divided into non-AS group and AS group. The AS group was further categorized: 2.6 ≤ AV-Vel < 3.0 m/s, mild AS; 3.0 ≤ AV-Vel < 4.0 m/s, moderate AS; and AV-Vel ≥ 4.0 m/s, severe AS. The primary outcome was all-cause mortality, and the secondary outcome was major adverse cardiovascular events (MACE), defined as a composite of all-cause mortality, myocardial infarction, or stroke. Multivariable Cox proportional hazards analysis was performed over 5-year observation period, with landmark analyses conducted at 30 days after PCI and from day 31 after PCI to 5 years. In total, 9,690 patients were analyzed (AS group, n = 361). Over a median follow-up of 2.57 (IQR: 0.89–4.24) years, AS group exhibited higher rates of mortality (HR: 3.06; 95% CI: 2.41–3.90; p < 0.001) and MACE (HR: 2.45; 95%CI: 1.97–3.04; p < 0.001) compared with non-AS group. Subgroup analysis revealed that patients with moderate and severe AS had worse short-term mortality and MACE within 30 days after PCI than the non-AS group, while patients with mild to severe AS showed significantly worse long-term outcomes than the non-AS group. Conclusions: AV-Vel is independently associated with both short- and long-term outcomes in patients undergoing PCI.
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Suzuki T, Nejima R, Inoue T, Kaji Y, Hattori T, Hoshi S, Todokoro D, Eguchi H, Nakai M, Inoue Y
Japanese journal of ophthalmology 2026年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Ophthalmology
Purpose: To compare physician-assessed and patient-reported outcomes quantified with the Japanese Ocular Surface Disease Index (J-OSDI) following the treatment of bacterial blepharitis and to evaluate the utility of the J-OSDI. Study design: Multicenter prospective observational study. Methods: Physicians assessed symptoms and findings, calculating clinical total scores at baseline (T0), 7 (T1) and 14 (T2) days post-treatment with 1% azithromycin ophthalmic solution, and 1 month after discontinuation (T3). Patients self-reported symptoms using the J-OSDI at these times. The J-OSDI score trends and differences in temporal changes between the J-OSDI and clinical total scores were analyzed by use of a linear mixed-effects model. Results: Forty-six eyes (46 patients; mean age, 71.8 years) were studied. The J-OSDI scores decreased significantly post-treatment for all the patients, with similar trends for both anterior and posterior blepharitis. For all the patients, the slope difference between the J-OSDI and clinical total scores was not significant in the T0–T1 period (P =.219), meaning that the J-OSDI scores reflected the clinical results, whereas it was significant in the T1–T2 (P =.004) and T2–T3 (P <.001) periods. The within-subject correlation between the 2 scores was 0.525 (95% CI 0.401–0.631). For anterior blepharitis, the slope differences were significant across all the periods, but for posterior blepharitis, no significant differences were observed in the T0–T1 or T1–T2 (P =.205, 0.06, respectively) periods, although significant differences were noted in the T2–T3 period (P =.018). Conclusion: The J-OSDI trajectory often diverges from physician-rated changes. Whilst the J-OSDI does not assess treatment response in anterior blepharitis, it may be partially reflective of improvement in posterior blepharitis.
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Reduced Left Atrial Reservoir Strain is Associated with Histopathologically Confirmed ANP-Amyloid Deposition. 査読あり 国際誌
Nishino S, Asada Y, Nishino C, Nakai M, Yokota A, Nishimura M, Yano M, Hatakeyama K, Shibata Y
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography 2026年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
BACKGROUND: Isolated atrial amyloidosis is characterized by atrial natriuretic peptide (ANP)-amyloid deposition confined to the atria and has been primarily linked to atrial fibrillation. However, its relationship with atrial mechanical function remains unclear. We investigated the association between left atrial reservoir strain (LASr) and histopathologically confirmed ANP-amyloid deposition. We also explored the potential clinical implications. METHODS: We retrospectively analyzed the available left atrial appendage tissue of 166 consecutive patients who underwent cardiac surgery. ANP-amyloid deposition was semi-quantitatively graded (0-3+) and categorized as negative (0-1+) or positive (2+-3+). Echocardiographic parameters were analyzed across grades. Multivariable logistic regression and sensitivity analyses were performed. The primary endpoint was a composite outcome comprising all-cause death, stroke or systemic embolism, and heart failure hospitalization. Perioperative and longitudinal clinical outcomes were assessed. RESULTS: ANP-amyloid deposition was present in 51.2% of patients. LASr declined progressively across increasing amyloid grades, which indicated a graded inverse relationship (p for trend < 0.001). Multivariable analysis showed that lower LASr remained significantly associated with ANP-amyloid positivity (adjusted odds ratio 0.75 per 1% increase, 95% confidence interval 0.65-0.87; p < 0.001). Sensitivity analyses showed consistent results. Perioperative outcomes did not differ significantly between groups. During follow-up, ANP-amyloid positivity was associated with a higher incidence of the composite endpoint. This association was primarily driven by an increased risk of heart failure hospitalization, whereas all-cause mortality and thromboembolic events did not differ significantly between groups. CONCLUSIONS: In this surgical cohort, reduced LASr was associated with higher ANP-amyloid deposition as confirmed through histopathology. These findings support an association between atrial mechanical dysfunction and histopathologically confirmed localized atrial amyloid involvement. ANP-amyloid deposition was associated with a higher incidence of composite clinical events, predominantly driven by heart failure hospitalization, warranting further investigation.
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Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Reflects Global Pathophysiology and Predicts All-Cause Morbidity and Mortality in Patients With Fontan Circulation. 査読あり
Ohuchi H, Mori A, Morimoto Y, Kato Y, Fujimoto K, Iwasa T, Shiraishi I, Kurosaki K, Nakai M
Circulation journal : official journal of the Japanese Circulation Society advpub ( 0 ) 2026年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本循環器学会
<b><i>Background:</i></b> Mac-2 binding protein glycosylation isomer (M2BPGi) is a validated biomarker for liver fibrosis in chronic liver disease. We investigated the clinical significance of serum M2BPGi concentrations in patients with Fontan circulation.<b><i>Methods and Results:</i></b> We prospectively measured serum M2BPGi concentrations in 426 consecutive Fontan patients (mean [±SD] age 23±10 years) and analyzed their associations with patients’ pathophysiology, including Fontan-associated liver disease (FALD), as well as all-cause unplanned hospitalization (UPH) and mortality. M2BPGi concentrations were associated with a wide range of Fontan-related pathophysiological features, including characteristic Fontan hemodynamics, total bile acid concentrations, FALD indices such as hepatic fibrosis markers and ultrasonographic image abnormalities, and impaired renal function. Among these variables, older age at Fontan operation, hypoxemia, C-reactive protein, total bile acid levels, and indices of hepatic fibrosis were independently associated with higher M2BPGi concentrations (P<0.05–0.001). During follow-up after the M2BPGi evaluation, 68 patients experienced UPH and 14 patients died. Elevated M2BPGi concentrations were associated with a higher risk of UPH and all-cause mortality (P<0.0001 for both), independent of elevated B-type natriuretic peptide levels.<b><i>Conclusions:</i></b> Serum M2BPGi concentrations reflect both FALD pathophysiology and hemodynamic burden, serving as a strong prognostic biomarker. M2BPGi can be a valuable tool for risk stratification in patients with Fontan failure, including those with FALD.
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川崎病既往成人の重症心血管後遺症入院例の検討 JROAD-DPC研究
三谷 義英, 中井 陸運, 津田 悦子
日本成人先天性心疾患学会雑誌 15 ( 1 ) 131 - 131 2026年1月
記述言語：日本語 掲載種別：速報，短報，研究ノート等（学術雑誌） 出版者・発行元：(一社)日本成人先天性心疾患学会
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宮崎泌尿器癌データベース(MUCD)を用いた宮崎県医療圏別腎がん診断時の臨床的特徴と治療選択の地域差
木村 翔一, 中井 陸運, 寺田 直樹, 澤田 篤郎, 賀本 敏行
西日本泌尿器科学会総会抄録集 77回 215 - 215 2025年11月
記述言語：日本語 掲載種別：速報，短報，研究ノート等（学術雑誌） 出版者・発行元：(一社)西日本泌尿器科学会
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川崎病に対する急性期から遠隔期・成人期に至る医療の国際的展開 成人期川崎病の重症心血管後遺症の日本の疫学 JROAD-DPC研究
三谷 義英, 中井 陸運, 津田 悦子
日本小児循環器学会総会・学術集会抄録集 61回 III - 5 2025年7月
記述言語：英語 掲載種別：速報，短報，研究ノート等（学術雑誌） 出版者・発行元：(NPO)日本小児循環器学会
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抗血栓薬未使用の成人患者における血液血栓形成能の臨床的決定因子 健診でのT-TAS 01研究(Clinical Determinants of Blood Thrombogenicity in Antithrombotic Drug-naive Adults: A Total Thrombus-Formation Analysis System (T-TAS 01) Study at Health Checkup)
工藤 丈明, 松浦 祐之介, 中井 陸運, 小山 彰平, 岩切 弘直, 海北 幸一, 柴田 剛徳
日本循環器学会学術集会抄録集 89回 PJ51 - 3 2025年3月
記述言語：英語 掲載種別：速報，短報，研究ノート等（学術雑誌） 出版者・発行元：(一社)日本循環器学会
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No-Hidden AF Project: All-Miyazak Alignment of University Hospital, Medical Association and Local Government for Monitoring Subclinical Atrial Fibrillation(タイトル和訳中)
渡邉 望, 海北 幸一, 古川 貢之, 井手口 武史, 松浦 祐之介, 中井 陸運, 山下 篤, 渡邊 玲子, 名越 敏郎
日本循環器学会学術集会抄録集 89回 OJ28 - 2 2025年3月
記述言語：英語 掲載種別：速報，短報，研究ノート等（学術雑誌） 出版者・発行元：(一社)日本循環器学会
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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先天性心疾患を主体とする小児期発症の心血管難治性疾患の救命 率の向上、円滑な移行医療、成人期以降の予後改善を目指した総合的研究
研究課題/領域番号：24FC0201 2024年04月 - 2027年03月
厚生労働省 厚生科研 難治性疾患政策研究事業
担当区分：研究分担者
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抗血栓薬新時代の脳卒中診療リスクベネフィット：複数大規模データベースを用いた解析
研究課題/領域番号：23K27522 2024年04月 - 2027年03月
日本学術振興会 科学研究費基金 基盤研究(B)
豊田 一則, 宮本 恵宏, 古賀 政利, 中井 陸運, 吉村 壮平, 三輪 佳織
担当区分：研究代表者
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ビッグデータ・機械学習を用いたアブレーション治療の有効性・安全性予測モデルの作成
研究課題/領域番号：23K24623 2024年04月 - 2025年03月
日本学術振興会 科学研究費基金 基盤研究(B)
草野 研吾, 山根 禎一, 清水 渉, 中井 陸運, 岩永 善高
担当区分：研究代表者
2017年に始まった本邦で行われている不整脈に対するカテーテルアブレーション全例登録事業（J-AB）は27万件を超える前向き登録事業が継続中でアブレーションレジストリとしては世界最大である。このビッグデータを用い、再発率が高く、また世界的にも合併症が増加している心房細動アブレーションについて、患者背景・使用デバイス・アブレーション部位・使用薬剤などの因子と急性期合併症発生や急性期・退院時・1年後の手技成功に関して、機械学習を用いたアブレーションの安全性・有効性に関する予測モデルを作成し、外部検証を行う。この予測モデルによって、治療成績の向上が期待できるのみならず、現在、ガイドラインでも解決されていない高齢者、心不全患者、無症状患者へのアブレーションの妥当性が明らかとなり、治療適応の大きなジレンマに対応できることが期待される。また、J-ABレジストリデータの解析結果を他国のデータベースと比較することで、本邦のカテーテルアブレーション治療の診療実態をより客観的に評価することが可能と考えられるが、同様の報告は存在しない。本研究の目的は、J-ABレジストリデータと他国データベースを用いて、本邦におけるカテーテルアブレーションの合併症発生率とそのリスク要因を明らかにし、本邦でのアブレーション治療の安全性向上に役立てるためのエビデンスを創出することである。
本研究の特徴として、①解析内容については、JAB登録（通年調査）から取得可能な項目を使用しており、実現可能性が高い（Feasible）、②本邦におけるリスク因子を明らかにするとともに、他国と比較した成績を明らかにすることで、特にリスクが高い患者においてリスク低減させる方法が明らかになれば、今後の治療方法を改善することができる（Modifiable）、③中央解析のみである。以上の点で、倫理的に問題がない（Ethical）。 -
成人先天性心疾患診療体制の患者アウトカムへの影響：DPCデータを用いた検討
研究課題/領域番号：23K10089 2023年04月 - 2027年03月
日本学術振興会 科学研究費基金 基盤研究(C)
落合 亮太, 石津 智子, 中井 陸運, 仁田 学
担当区分：研究分担者
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抗血栓薬新時代の脳卒中診療リスクベネフィット：複数大規模データベースを用いた解析
研究課題/領域番号：23H02831 2023年04月 - 2027年03月
日本学術振興会 科学研究費助成事業 基盤研究(B)
豊田 一則, 宮本 恵宏, 古賀 政利, 中井 陸運, 吉村 壮平, 三輪 佳織, 田中 寛大
担当区分：研究分担者