Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2022.09

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  Sapporo Medical University   Department of Cardiovascular, Renal and Metabolic Medicine   Professor

Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

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  THE JAPAN ENDOCRINE SOCIETY

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  日本高血圧学会

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  国際高血圧学会

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  日本心血管内分泌代謝学会

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  日本心臓病学会

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Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Cardiology  

• Life sciences   Metabolism and endocrinology  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

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

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• 小胞体ストレス

• メタボリック症候群

• 高血圧

• 血管内皮

• 脂質異常症

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Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Machine learning-based analyses of contributing factors for the development of hypertension: a comparative study.

  Marenao Tanaka, Yukinori Akiyama, Kazuma Mori, Itaru Hosaka, Keisuke Endo, Toshifumi Ogawa, Tatsuya Sato, Toru Suzuki, Toshiyuki Yano, Hirofumi Ohnishi, Nagisa Hanawa, Masato Furuhashi

  Clinical and experimental hypertension (New York, N.Y. : 1993)   47 ( 1 ) 2449613 - 2449613  2025.12  [International journal]

  　View Summary

  OBJECTIVES: Sufficient attention has not been given to machine learning (ML) models using longitudinal data for investigating important predictors of new onset of hypertension. We investigated the predictive ability of several ML models for the development of hypertension. METHODS: A total of 15 965 Japanese participants (men/women: 9,466/6,499, mean age: 45 years) who received annual health examinations were randomly divided into a training group (70%, n = 11,175) and a test group (30%, n = 4,790). The predictive abilities of 58 candidates including fatty liver index (FLI), which is calculated by using body mass index, waist circumference and levels of γ-glutamyl transferase and triglycerides, were investigated by statistics analogous to the area under the curve (AUC) in receiver operating characteristic curve analyses using ML models including logistic regression, random forest, naïve Bayes, extreme gradient boosting and artificial neural network. RESULTS: During a 10-year period (mean period: 6.1 years), 2,132 subjects (19.1%) in the training group and 917 subjects (19.1%) in the test group had new onset of hypertension. Among the 58 parameters, systolic blood pressure, age and FLI were identified as important candidates by random forest feature selection with 10-fold cross-validation. The AUCs of ML models were 0.765-0.825, and discriminatory capacity was significantly improved in the artificial neural network model compared to that in the logistic regression model. CONCLUSIONS: The development of hypertension can be simply and accurately predicted by each ML model using systolic blood pressure, age and FLI as selected features. By building multiple ML models, more practical prediction might be possible.

  DOI PubMed

• Can small dense LDL cholesterol be estimated from the lipid profile?

  Tatsuya Sato, Marenao Tanaka, Masato Furuhashi

  Current opinion in lipidology    2025.04  [International journal]

  　View Summary

  PURPOSE OF REVIEW: Small dense low-density lipoprotein cholesterol (sdLDL-C) is recognized for its strong atherosclerogenic potential. However, its direct measurement remains impractical in clinical settings due to its high cost, time constraints, and labor-intensive nature. This review discusses the benefits and limitations of estimating sdLDL-C using conventional lipid fractions, highlighting recent advancements in estimation methods. RECENT FINDINGS: Sampson et al. proposed a novel equation for estimating sdLDL-C based on conventional lipid parameters, offering a more accessible alternative to direct measurement. Recent studies, including ours, demonstrated that this estimation method achieves sufficiently high accuracy for overall application. However, its accuracy can be improved by incorporating machine learning. Furthermore, sdLDL-C estimated by Sampson's equation has been shown to be a superior risk marker for hypertension, an intermediate phenotype of atherosclerosis, and ischemic heart disease, a major cardiovascular event, compared to conventional lipid profiles alone, although further research is needed to determine whether estimated sdLDL-C is equivalent to directly measured sdLDL-C in risk assessment. SUMMARY: Estimated sdLDL-C presents a promising alternative to direct measurement. While estimated sdLDL-C levels can serve a risk marker for cardiovascular diseases, further research is needed to refine estimation models and explore their integration into clinical practice.

  DOI PubMed

• Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Is an Independent Risk Factor for the Development of Ischemic Heart Disease ― A 10-Year Cohort Study ―

  Toshifumi Ogawa, Tatsuya Sato, Marenao Tanaka, Yukinori Akiyama, Kei Nakata, Hidemichi Kouzu, Kazuma Mori, Hiroki Aida, Wataru Kawaharata, Itaru Hosaka, Toru Suzuki, Nagisa Hanawa, Masato Furuhashi

  Circulation Reports ( Japanese Circulation Society )   2025.04

  DOI

• High Level of Estimated Small Dense Low-Density Lipoprotein Cholesterol as an Independent Risk Factor for the Development of Ischemic Heart Disease Regardless of Low-Density Lipoprotein Cholesterol Level ― A 10-Year Cohort Study ―

  Keisuke Endo, Marenao Tanaka, Tatsuya Sato, Masafumi Inyaku, Kei Nakata, Wataru Kawaharata, Hiroki Aida, Itaru Hosaka, Yukinori Akiyama, Nagisa Hanawa, Masato Furuhashi

  Circulation Journal ( Japanese Circulation Society )   2025.03

  DOI

• Elevated urinary fatty acid-binding protein 4 level predicts future renal dysfunction and poor prognosis in Japanese patients with diabetes: a longitudinal cohort study

  Marenao Tanaka, Tatsuya Sato, Tomohito Gohda, Nozomu Kamei, Maki Murakoshi, Erika Ishiwata, Kei Nakata, Yukinori Akiyama, Keisuke Endo, Wataru Kawaharata, Hiroki Aida, Toru Suzuki, Mitsunobu Kubota, Michiyoshi Sanuki, Yusuke Suzuki, Masato Furuhashi

  Clinical Kidney Journal ( Oxford University Press (OUP) )   2025.03

  　View Summary

  Abstract Background Fatty acid-binding protein 4 (FABP4) is an adipokine secreted from adipocytes and macrophages and is also expressed in injured, but not normal, glomerular endothelial cells. Elevated levels of urinary FABP4 (U-FABP4) have been reported to be associated with glomerular damage and increased proteinuria. Methods The associations of levels of U-FABP4 at baseline with future events including renal dysfunction defined by a 30% decline in estimated glomerular filtration rate (eGFR) and all-cause death were investigated in 660 patients with diabetes (type 1/2: 57/603). Results During a follow-up period (median: 62 months), 90 patients (13.6%) developed renal dysfunction, and 66 patients (10.0%) died (median follow-up period: 65 months). Kaplan-Meier survival curves showed that there were significant differences in cumulative incidences for a 30% decline in eGFR and all-cause death in patients divided by the tertiles of U-FABP4 level. Furthermore, multivariable Cox proportional hazard models with a restricted cubic spline showed that hazard ratios for a 30% decline in eGFR and all-cause death increased with a higher level of logarithmically transformed (Log) U-FABP4 after adjustment for age, sex, type of diabetes, body mass index, current smoking habit, duration of diabetes, comorbidities of hypertension and dyslipidemia, eGFR and the categorical classification of urinary albumin-creatinine ratio. The addition of Log U-FABP4 to traditional risk factors significantly increased the discriminatory capacities for renal dysfunction in net reclassification improvement (NRI) and integrated discrimination improvement and for all-cause death in NRI. Conclusion U-FABP4 is a predictive biomarker for future renal dysfunction and poor prognosis in patients with diabetes.

  DOI

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 肥満減量術後慢性期の血糖コントロール悪化にセマグルチドが著効した2型糖尿病の症例

  赤澤史子, 小川俊史, 中田圭, 佐藤達也, 伊東竜哉, 竹政伊知朗, 古橋眞人

  糖尿病(Web)   67 ( 1 )  2024

  J-GLOBAL

• Small dense LDLコレステロールの推定式の検証と臨床的意義の検討

  遠藤圭佑, 田中希尚, 田中希尚, 佐藤達也, 佐藤達也, 秋山幸功, 小林亮, 田中真輝人, 保坂到, 古橋眞人, 中田圭, 中田圭, 小山雅之, 小山雅之, 大西浩文, 大西浩文, 高橋聡

  日本動脈硬化学会総会・学術集会プログラム・抄録集(Web)   56th  2024

  J-GLOBAL

• 腹部大動脈瘤拡大因子としての瘤壁三次リンパ組織形成および濾胞関連新規リンパ球サブセットの解明

  保坂到, 池上一平, 三上拓真, 佐藤達也, 小川俊文, 武川慶, 田中希尚, 遠藤圭佑, 秋山幸功, 大川陽史, 仲澤順二, 柴田豪, 中島智博, 伊庭裕, 高野賢一, 一宮慎吾, 川原田修義, 古橋眞人

  脈管学(Web)   64 ( Supplement )  2024

  J-GLOBAL

• Graph based clusteringを用いた腹部大動脈瘤拡大因子としての濾胞関連新規リンパ球サブセットの同定と機能的意義の解明

  保坂到, 池上一平, 三上拓真, 佐藤達也, 小川俊文, 田中希尚, 遠藤圭佑, 秋山幸功, 大川陽史, 仲澤順二, 柴田豪, 中島智博, 伊庭裕, 高野賢一, 一宮慎吾, 川原田修義, 古橋眞人

  脈管学(Web)   64 ( Supplement )  2024

  J-GLOBAL

• Saphenous vein harvesting: Meta-analysis, metaflammation, and adipose tissue remodeling

  Masato Furuhashi, Takuma Mikami, Nobuyoshi Kawaharada, Michael R. Dashwood

  Journal of Cardiac Surgery ( John Wiley and Sons Inc )  36 ( 12 ) 4832 - 4833  2021.12

  Rapid communication, short report, research note, etc. (scientific journal)  

  DOI PubMed

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Awards 【 display / non-display 】

Awards 【 display / non-display 】

• 五島雄一郎賞

  2018   第50回日本動脈硬化学会  

  Winner： 古橋 眞人

• 学術奨励賞

  2014   第35回日本肥満学会  

  Winner： 古橋眞人

• 学術賞

  2013   第36回日本高血圧学会  

  Winner： 古橋眞人

• 高峰譲吉研究奨励賞

  2012   第16回日本心血管内分泌代謝学会  

  Winner： 古橋眞人

• CPIS (Cardiovascular Pharmacotherapy International Symposium) 賞

  2008   第72回日本循環器学会  

  Winner： 古橋眞人

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 脂質シャペロンと代謝性脂肪肝疾患が関わる腎臓病発症機序の解明

  基盤研究(C)

  Project Year :

  2022.04

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  2025.03

   

  田中 希尚, 古橋 眞人

• The association of PCSK7 with coronary calcification

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2020.04

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  2024.03

   

  片岡 有, 古橋 眞人, 小倉 正恒

  　View Summary

  心筋梗塞の原因となる冠動脈石灰化の特徴を解析し、論文報告した。 Atherosclerosis. 2021 Feb;318:70-75. 675例の心筋梗塞症例を解析した。 心筋梗塞を引き起こす冠動脈石灰化は、心臓死や再狭窄、心筋梗塞再発リスクが高いことを報告した。 JACC Case Rep. 2020 Sep 2;2(12):1872-1878.

• Elucidation of intracellular actions of fatty acid-binding protein family and application to clinical therapies

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2020.04

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  2023.03

   

  古橋 眞人

  　View Summary

  1.ヒト脂肪組織由来幹細胞にリコンビナントFABP4を外因性に投与し、RNA-seqを行った。蛋白~蛋白相互作用カスケード解析から様々な転写因子および 各種キナーゼとの相互作用が認められた。 2.ヒト脂肪組織由来幹細胞にリコンビナントFABP4を外因性に投与し、CE-TOFMSおよびLC-TOFMSを用いてメタボローム解析を行った。FABP4の外因性投与により、 様々な細胞内メタボライトの変化が認められ、FABP4が脂肪細胞由来の生理活性物質であるアディポカインとして働くことが確認された。 3.リコンビナントFABP4に対する各種脂肪酸(パルミチン酸、パルミトレイン酸、ステアリン酸、オレイン酸、リノール酸、αリノレイン酸、アラキドン酸、エ イコサペンタエン酸、ドコサヘキサエン酸)に対する脂肪酸結合親和性を1-anilinonapthalene 8-sulfonic acid (1,8 ANS)を用いて行ったところ、通常状態で は脂肪酸結合親和性は必須脂肪酸で、多価不飽和脂肪酸であるリノール酸やαリノレイン酸に親和性が高く、飽和脂肪酸であるパルミチン酸とは親和性が低かった。また、酸化ストレスを模倣するフリーラジカルジェネレーターである2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)の存在下ではパルミチン酸 以外の脂肪酸はKd値が上昇し、親和性が相対的に低くなったが、パルミチン酸とのKd値は変化がなかった。 4. リコンビナントFABP4を各種細胞に投与して、炎症関連分子の変化を確認した。 5.疫学調査 (端野・壮瞥町研究) でFABP4濃度を測定し、12年間のフォロー期間中の心血管死と関連することを見出した。 6.ヒトの心臓手術時に採取した心外膜脂肪組織や血管周囲脂肪組織の検討からFABP4の発現を確認した。

• Elucidation of underlying mechanism of the onset and renal deterioration of kidney disease contributed by lipid chaperones

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2019.04

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  2022.03

   

  Marenao Tanaka

  　View Summary

  In a renal biopsy cohort, urinary FABP4 excretion was associated with renal function, urinary protein levels and deterioration of renal function after 1 year. In a general population cohort, a high LDL-cholesterol level was negatively associated with change in eGFR during 10-year follow-up period and was a risk factor for the development of CKD in males. In IgA nephropathy and gddY, a IgAN-prone mouse model, expression of FABP4 was ectopically induced by glomerular injury in cells of the glomerulus including glomerular endothelial cells and macrophages, and the extent of glomerular FABP4 expression was associated with proteinuria and renal dysfunction. Expression of ER stress markers were present on the cells in glomerulus in IgAN and in gddY. In human renal glomerular endothelial cells, FABP4 was induced by treatment with VEGF and was secreted from cells. Treatment of podocytes with FABP4 significantly increased gene expression of inflammatory cytokines and ER stress markers.

• Elucidation of ectopic expression of fatty acid-binding protein 4 in endovascular injury and application to clinical therapies

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2017.04

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  2020.03

   

  Furuhashi Masato

  　View Summary

  Fatty acid-binding protein 4 (FABP4) is expressed in adipocytes and macrophages and plays significant roles in the development of insulin resistance and atherosclerosis. The present study demonstrated that FABP4 was ectopically induced in endothelial cells by cellular senescence and vascular injury. Furthermore, secreted FABP4 from injured vascular endothelial cells promoted inflammatory response in several cells, proliferation and migration in vascular smooth muscle cells, and endothelial dysfunction in vascular endothelial cells, leading to the development of neointima formation after vascular injury.

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