研 究

本講座では、徳島大学病院と阿南医療センターの診療を通じて、効果的な糖尿病・代謝疾患診療の推進に加えて、基礎および臨床面での病態解明と治療の開発研究を行うことを大きな使命としています。
研究テーマとしては以下の3つの柱で進めていきます。

(1)(1) 生活習慣病モデル動物の解析や臨床サンプルを用いたバイオマーカー解析により、糖尿病・代謝疾患病態および血管合併症の発症機序解明

遺伝子改変動物を用いて、代謝・循環改善薬の介入による代謝変化や動脈硬化症の予防効果の検証・病態解明を行う他、受診患者さんの臨床サンプルや臨床データを解析することで、効果的な治療法の開発を行います。特に妊娠期の糖代謝異常は、胎児の死亡や先天奇形、巨大児分娩また母体についても合併症の増加や分娩後に顕性糖尿病の発症を招くことが知られており医学上解決すべき重要な課題の一つですがその病態は十分には明らかになっていません。我々は独自の視点で新たな病態の同定と検査マーカーの開発を行います。

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(2)生活習慣病患者における早期動脈硬化病変の検出と治療介入の効果検証

受診患者さんの早期動脈硬化症の病態検出目的と心血管合併症発症や予後予測の強力なエビデンスを有する血管内皮機能検査(FMD)の積極的な導入を行い、FMDの正常化を目指した病態解析や治療法の開発を行います。現在FMD測定装置を阿南共栄病院に設置し、徳島大学病院においても新型のFMD測定装置の導入を行う予定です。臨床研究計画の承認を徳島大学病院および阿南共栄病院の両倫理委員会で承認を受け、対象患者のエントリーを開始しました。

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(3)高齢者糖尿病・代謝疾患患者に対する医療や在宅医療を含め、地域包括ケアシステムの中での新たアプローチによる診療方法の開発

高齢化が進み医療支援が今後困難となることが予想される地域において、増加の一途である糖尿病・代謝疾患診療をいかに効率的かつ安全に行っていくかという課題について行政と協力しつつ対策を講じて行きます。

欧文論文業績

2017年の業績

• Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus.
  Yagi S, Hirata Y, Ise T, Kusunose K, Yamada H, Fukuda D, Salim HM, Maimaituxun G, Nishio S, Takagawa Y, Hama S, Matsuura T, Yamaguchi K, Tobiume T, Soeki T, Wakatsuki T, Aihara K, Akaike M, Shimabukuro M, Sata M. Diabetol Metab Syndr. 2017 Oct 4;9:78. doi: 10.1186/s13098-017-0275-4. eCollection 2017. PubMed PMID: 29034006; PubMed Central PMCID: PMC5628447.
• Improved Exercise Capacity After Cardiac Rehabilitation Is Associated with Reduced Visceral Fat in Patients with Chronic Heart Failure.
  Takagawa Y, Yagi S, Ise T, Ishii A, Nishikawa K, Fukuda D, Kusunose K, Matsuura T, Tobiume T, Yamaguchi K, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Katoh S, Aihara K, Akaike M, Sata M. Int Heart J. 2017 Oct 21;58(5):746-751. doi: 10.1536/ihj.16-454. Epub 2017 Sep 30. PubMed PMID: 28966316.
• Low Serum Levels of Eicosapentaenoic Acid and Docosahexaenoic Acid are Risk Factors for Cardiogenic Syncope in Patients with Brugada Syndrome.
  Yagi S, Soeki T, Aihara K, Fukuda D, Ise T, Kadota M, Bando S, Matsuura T, Tobiume T, Yamaguchi K, Kusunose K, Yamada H, Wakatsuki T, Shimabukuro M, Akaike M, Sata M. Int Heart J. 2017 Oct 21;58(5):720-723. doi: 10.1536/ihj.16-278. Epub 2017 Sep 30. PubMed PMID: 28966307.
• Dietary iron restriction alleviates renal tubulointerstitial injury induced by protein overload in mice.
  Ikeda Y, Horinouchi Y, Hamano H, Hirayama T, Kishi S, Izawa-Ishizawa Y, Imanishi M, Zamami Y, Takechi K, Miyamoto L, Ishizawa K, Aihara K, Nagasawa H, Tsuchiya K, Tamaki T. Sci Rep. 2017 Sep 6;7(1):10621. doi: 10.1038/s41598-017-11089-0. PubMed PMID: 28878231; PubMed Central PMCID: PMC5587788.
• Promising Nutrients for Preventing Cardiovascular Disease.
  Yagi S, Fukuda D, Aihara K, Akaike M, Shimabukuro M, Sata M. n-3 Polyunsaturated Fatty Acids: J Atheroscler Thromb. 2017 Oct 1;24(10):999-1010. doi:10.5551/jat.RV17013. Epub 2017 Aug 24. PubMed PMID: 28835582; PubMed Central PMCID: PMC5656772.
• The Role of Heparin Cofactor Ⅱ in the Regulation of Insulin Sensitivity and Maintenance of Glucose Homeostasis in Humans and Mice.
  Kurahashi K, Inoue S, Yoshida S, Ikeda Y, Morimoto K, Uemoto R, Ishikawa K, Kondo T, Yuasa T, Endo I, Miyake M, Oyadomari S, Matsumoto T, Abe M, Sakaue H, Aihara K. J Atheroscler Thromb. 2017 Dec 1;24(12):1215-1230. doi: 10.5551/jat.37739. Epub 2017 May 15. PubMed PMID: 28502917; PubMed Central PMCID: PMC5742367.
• Remarkable Shrinkage of a Growth Hormone (GH)-secreting Macroadenoma Induced by Somatostatin Analogue Administration: A Case Report and Literature Review.
  Kurahashi K, Endo I, Kondo T, Morimoto K, Yoshida S, Kuroda A, Aihara K, Matsuhisa M, Nakajima K, Mizobuchi Y, Nagahiro S, Abe M, Fukumoto S. Intern Med. 2017 Sep 15;56(18):2455-2461. doi: 10.2169/internalmedicine.8223-16. Epub 2017 Aug 21. PubMed PMID: 28824054; PubMed Central PMCID: PMC5643174.

2016年の業績

• A vicious cycle between acid sensing and survival signaling in myeloma cells: acid-induced epigenetic alteration.
  Amachi R, Hiasa M, Teramachi J, Harada T, Oda A, Nakamura S, Hanson D, Watanabe K, Fujii S, Miki H, Kagawa K, Iwasa M, Endo I, Kondo T, Yoshida S, Aihara K, Kurahashi K, Kuroda Y, Horikawa H, Tanaka E, Matsumoto T, Abe M. Oncotarget. 2016 Oct 25;7(43):70447-70461. doi: 10.18632/oncotarget.11927. PubMed PMID: 27626482; PubMed Central PMCID: PMC5342564.
• Sequential cleavage of insulin receptor by calpain 2 and γ-secretase impairs insulin signalling.
  Yuasa T, Amo-Shiinoki K, Ishikura S, Takahara M, Matsuoka T, Kaneto H, Kuroda A, Matsuhisa M, Hashida S.
  Diabetologia. 2016;59(12):2711-2721. PubMed PMID: 27695899.
• Serum carboxy-terminal telopeptide of type I collagen levels are associated with carotid atherosclerosis in patients with cardiovascular risk factors.
  Kondo T, Endo I, Aihara K, Onishi Y, Dong B, Ohguro Y, Kurahashi K, Yoshida S, Fujinaka Y, Kuroda A, Matsuhisa M, Fukumoto S, Matsumoto T, Abe M.
  Endocr J. 2016;63(4):397-404. doi: 10.1507/endocrj.EJ15-0589. PubMed PMID: 26877258.
• Suppression of the Hypothalamic-pituitary-adrenal Axis by Maximum Androgen Blockade in a Patient with Prostate Cancer.
  Kondo T, Endo I, Ooguro Y, Morimoto K, Kurahashi K, Yoshida S, Kuroda A, Aihara KI, Matsuhisa M, Abe M, Fukumoto S. Intern Med. 2016;55(24):3623-3626. Epub 2016 Dec 15.
• Roles of the Androgen-Androgen Receptor System in Vascular Angiogenesis.
  Yoshida S, Ikeda Y, Aihara K.
  J Atheroscler Thromb. 2016;23(3):257-65. doi:10.5551/jat.31047. PubMed PMID: 26522430.

2015年の業績

• Factor VII Tokushima: the first case of factor VII Cys22Gly with the development of myocardial infarction in the proband receiving recombinant factor VIIa replacement therapy.
  Shigekiyo T, Sekimoto E, Shibata H, Ozaki S, Okumura T, Fujinaga H, Shibata H, Aihara K, Akaike M.
  Blood Coagul Fibrinolysis. 2015 Dec;26(8):956-8. doi: 10.1097/MBC.0000000000000346.
  PMID: 26517065
• Roles of the Androgen - Androgen Receptor System in Vascular Angiogenesis.
  Yoshida S, Ikeda Y, Aihara K.
  J Atheroscler Thromb. 2015 Oct 30.
  [Epub ahead of print] PubMed PMID: 26522430.
• Reduced ratio of eicosapentaenoic acid and docosahexaenoic acid to arachidonic acid is associated with early onset of acute coronary syndrome.
  Yagi S, Aihara K, Fukuda D, Takashima A, Bando M, Hara T, Nishimoto S, Ise T, Kusunose K, Yamaguchi K, Tobiume T, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Akaike M, Sata M.
  Nutr J. 2015 Oct 29;14:111. doi: 10.1186/s12937-015-0102-4.
• Predictive Factors for Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus.
  Yagi S, Aihara K, Akaike M, Fukuda D, Salim HM, Ishida M, Matsuura T, Ise T, Yamaguchi K, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Matsumoto T, Sata M.
  Diabetes Metab J. 2015 Aug;39(4):342-7. doi: 10.4093/dmj.2015.39.4.342. Epub 2015 Jul 21.
  PMID: 26301197
• Overexpression of insulin receptor partially improves obese and diabetic phenotypes in db/db mice.
  Sasaki T, Kuroko M, Sekine S, Matsui S, Kikuchi O, Susanti VY, Kobayashi M, Tanaka Y, Yuasa T, Kitamura T.
  Endocr J.2015;62(9):787-96. doi: 10.1507/endocrj.EJ15-0255.
  Epub 2015 Jun 20.
  PubMed PMID: 26096452.
• Non-invasive Measurement of Skin Autofluorescence as a Beneficial Surrogate Marker for Atherosclerosis in Patients with Type 2 Diabetes.
  Temma J, Matsuhisa M, Horie T, Kuroda A, Mori H, Tamaki M, Endo I, Aihara K, Abe M, Matsumoto T.
  J Med Invest. 2015;62(3-4):126-9. doi: 10.2152/jmi.62.126.
• Bilirubin exerts pro-angiogenic property through Akt-eNOS-dependent pathway.
  Ikeda Y, Hamano H, Satoh A, Horinouchi Y, Izawa-Ishizawa Y, Kihira Y, Ishizawa K, Aihara K, Tsuchiya K, Tamaki T.
  Hypertens Res. 2015 Nov;38(11):733-40. doi: 10.1038/hr.2015.74. Epub 2015 Jul 2.
  PMID: 26134126
• Effect of combination tablets containing amlodipine 10 mg and irbesartan 100 mg on blood pressure and cardiovascular risk factors in patients with hypertension.
  Yagi S, Takashima A, Mitsugi M, Wada T, Hotchi J, Aihara K, Hara T, Ishida M, Fukuda D, Ise T, Yamaguchi K, Tobiume T, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Akaike M, Sata M.
  Ther Clin Risk Manag. 2015 Jan 12;11:83-8. doi: 10.2147/TCRM.S72299. eCollection 2015.
  PMID: 25624765

2014年の業績

• Serum concentration of eicosapentaenoic acid is associated with cognitive function in patients with coronary artery disease.
  Yagi S, Hara T, Ueno R, Aihara K, Fukuda D, Takashima A, Hotchi J, Ise T, Yamaguchi K, Tobiume T, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Akaike M, Sata M.
  Nutr J. 2014 Dec 4;13(1):112. doi: 10.1186/1475-2891-13-112.
  PMID: 25471307
• Anti-albuminuric effect of the aldosterone blocker eplerenone in non-diabetic hypertensive patients with albuminuria: a double-blind, randomised, placebo-controlled trial.
  Ando K, Ohtsu H, Uchida S, Kaname S, Arakawa Y, Fujita T; EVALUATE Study Group (including Aihara K).
  Lancet Diabetes Endocrinol. 2014 Dec;2(12):944-53. Erratum in: Lancet Diabetes Endocrinol. 2015 Apr;3(4):e3.
  PMID: 25466242
• An antiangiogenic isoform of VEGF-A contributes to impaired vascularization in peripheral artery disease.
  Kikuchi R, Nakamura K, MacLauchlan S, Ngo DT, Shimizu I, Fuster JJ, Katanasaka Y, Yoshida S, Qiu Y, Yamaguchi TP, Matsushita T, Murohara T, Gokce N, Bates DO, Hamburg NM, Walsh K.
  Nat Med. 2014 Dec;20(12):1464-71. doi: 10.1038/nm.3703. Epub 2014 Nov 2.
  PMID: 25362254
• Effects of docosahexaenoic Acid on the endothelial function in patients with coronary artery disease
  Yagi S, Aihara K, Fukuda D, Takashima A, Hara T, Hotchi J, Ise T, Yamaguchi K, Tobiume T, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Akaike M, Sata M.
  J Atheroscler Thromb. 2015;22(5):447-54. doi:10.5551/jat.26914.
  Epub 2014 Oct 24.
  PubMed PMID: 25342567.
• Adiponectin attenuates abdominal aortic aneurysm formation in hyperlipidemic mice.
  Atherosclerosis. 2014 Aug;235(2):339-46. doi: 10.1016/j.atherosclerosis.2014.05.923. Epub 2014 May 23.
  PMID: 24911638
• High serum parathyroid hormone and calcium are risk factors for hypertension in Japanese patients.
  Yagi S, Aihara K, Kondo T, Endo I, Hotchi J, Ise T, Iwase T, Akaike M, Matsumoto T, Sata M.
  Endocr J. 2014;61(7):727-33. Epub 2014 May 22.
  PMID: 24849536
• Antithrombin-p.Ala416Pro: the second reported case in Japan.
  Shigekiyo T, Sekimoto E, Shibata H, Ozaki S, Kurushima A, Aihara K.
  Intern Med. 2014;53(5):477-81.
  PMID: 24583439
• Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells.
  Yuasa T, Amo K, Ishikura S, Nagaya H, Uchiyama K, Hashida S, Ebina Y.
  Biochem Biophys Res Commun. 2014 Feb 28;445(1):236-43. doi: 10.1016/j.bbrc.2014.01.187. Epub 2014 Feb 6.
  PMID: 24508798
• Association of lower limb muscle mass and energy expenditure with visceral fat mass in healthy men.
  Yagi S, Kadota M, Aihara K, Nishikawa K, Hara T, Ise T, Ueda Y, Iwase T, Akaike M, Shimabukuro M, Katoh S, Sata M.
  Diabetol Metab Syndr. 2014 Feb 26;6(1):27. doi: 10.1186/1758-5996-6-27.
  PMID: 24571923
• Diabetic conditions differentially affect the endothelial function, arterial stiffness and carotid atherosclerosis.
  Kinouchi M, Aihara K, Fujinaka Y, Yoshida S, Ooguro Y, Kurahashi K, Kondo T, Aki N, Kuroda A, Endo I, Matsuhisa M, Matsumoto T.
  J Atheroscler Thromb. 2014;21(5):486-500. Epub 2014 Jan 8.
  PMID: 24401746

2013年の業績

• Androgen receptor promotes sex-independent angiogenesis in response to ischemia and is required for activation of vascular endothelial growth factor receptor signaling.
  Yoshida S, Aihara K, Ikeda Y, Sumitomo-Ueda Y, Uemoto R, Ishikawa K, Ise T, Yagi S, Iwase T, Mouri Y, Sakari M, Matsumoto T, Takeyama K, Akaike M, Matsumoto M, Sata M, Walsh K, Kato S, Matsumoto T.
  Circulation. 2013 Jul 2;128(1):60-71. doi: 10.1161/CIRCULATIONAHA.113.001533. Epub 2013 May 30.
  PMID: 23723256
• T-cadherin is essential for adiponectin-mediated revascularization.
  Parker-Duffen JL, Nakamura K, Silver M, Kikuchi R, Tigges U, Yoshida S, Denzel MS, Ranscht B, Walsh K.
  J Biol Chem. 2013 Aug 23;288(34):24886-97. doi: 10.1074/jbc.M113.454835. Epub 2013 Jul 3.
  PMID: 23824191
• Bovine milk-derived lactoferrin exerts proangiogenic effects in an Src-Akt-eNOS-dependent manner in response to ischemia.
  Ikeda Y, Tajima S, Izawa-Ishizawa Y, Kihira Y, Ishizawa K, Yoshida S, Aihara K, Tsuchiya K, Tamaki T.
  J Cardiovasc Pharmacol. 2013 May;61(5):423-9. doi: 10.1097/FJC.0b013e318287d526.
  PMID: 23364610
• Serum carboxy-terminal telopeptide of type I collagen (ICTP) as a surrogate marker for vulnerable plaques in atherosclerotic patients: a pilot study.
  Kato S, Endo I, Fujimura M, Kuriwaka-Kido R, Fujinaka Y, Aihara K, Iwase T, Inoue D, Akaike M, Abe M, Matsumoto T.
  Atherosclerosis. 2013 Jul;229(1):182-5. doi: 10.1016/j.atherosclerosis.2013.03.030. Epub 2013 Apr 6.
  PMID: 23639859
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• Vitamin D receptor in osteoblasts is a negative regulator of bone mass control.
  Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K, Sato T, Kawano H, Aihara K, Nakamichi Y, Watanabe T, Shindo M, Inoue K, Inoue E, Tsuji N, Hoshino M, Karsenty G, Metzger D, Chambon P, Kato S, Imai Y.
  Endocrinology. 2013 Mar;154(3):1008-20. doi: 10.1210/en.2012-1542. Epub 2013 Feb 6.
  PMID: 23389957

2012年の業績

• Carbohydrate-to-insulin ratio is estimated from 300-400 divided by total daily insulin dose in type 1 diabetes patients who use the insulin pump.
  Kuroda A, Yasuda T, Takahara M, Sakamoto F, Kasami R, Miyashita K, Yoshida S, Kondo E, Aihara K, Endo I, Matsuoka TA, Kaneto H, Matsumoto T, Shimomura I, Matsuhisa M.
  Diabetes Technol Ther. 2012 Nov;14(11):1077-80. doi: 10.1089/dia.2012.0109.
  PMID: 23101953
• Nitrosonifedipine ameliorates angiotensin II-induced vascular remodeling via antioxidative effects.
  Sakurada T, Ishizawa K, Imanishi M, Izawa-Ishizawa Y, Fujii S, Tominaga E, Tsuneishi T, Horinouchi Y, Kihira Y, Ikeda Y, Tomita S, Aihara K, Minakuchi K, Tsuchiya K, Tamaki T.
  Naunyn Schmiedebergs Arch Pharmacol. 2013 Jan;386(1):29-39. doi: 10.1007/s00210-012-0810-7. Epub 2012 Nov 14.
  PMID: 23149861
• Inflammation and vascular remodeling.
  Aihara K, Mogi M, Shibata R, Bishop-Bailey D, Reilly MP.
  Int J Vasc Med. 2012;2012:596796. doi: 10.1155/2012/596796. Epub 2012 Nov 13. No abstract available.
  PMID: 23209907
• Heparin cofactor II, a serine protease inhibitor, promotes angiogenesis via activation of the AMP-activated protein kinase-endothelial nitric-oxide synthase signaling pathway.
  Ikeda Y, Aihara K, Yoshida S, Iwase T, Tajima S, Izawa-Ishizawa Y, Kihira Y, Ishizawa K, Tomita S, Tsuchiya K, Sata M, Akaike M, Kato S, Matsumoto T, Tamaki T.
  J Biol Chem. 2012 Oct 5;287(41):34256-63. doi: 10.1074/jbc.M112.353532. Epub 2012 Aug 17.
  PMID: 22904320
• Fibrinogen Tokushima II: a new case of congenital dysfibrinogenemia with a γ methionine-310 to threonine substitution.
  Shigekiyo T, Sekimoto E, Shirakami A, Yamaguchi H, Shibata H, Ozaki S, Maegawa M, Aihara K.
  Int J Hematol. 2012 Sep;96(3):395-7. doi: 10.1007/s12185-012-1148-0. Epub 2012 Jul 27. No abstract available.
  PMID: 22836217
• Effects of statins on cardiorenal syndrome.
  Yagi S, Aihara K, Ikeda Y, Akaike M, Sata M, Matsumoto T.
  Int J Vasc Med. 2012;2012:162545. doi: 10.1155/2012/162545. Epub 2012 Jun 26.
  PMID: 22792467
• Effects of androgens on cardiovascular remodeling.
  Ikeda Y, Aihara K, Yoshida S, Akaike M, Matsumoto T.
  J Endocrinol. 2012 Jul;214(1):1-10. doi: 10.1530/JOE-12-0126. Epub 2012 Apr 5. Review.
  PMID: 22493003

2011年の業績

• Ezetimibe monotherapy ameliorates vascular function in patients with hypercholesterolemia through decreasing oxidative stress.
  Kurobe H, Aihara K, Higashida M, Hirata Y, Nishiya M, Matsuoka Y, Kanbara T, Nakayama T, Kinoshita H, Sugano M, Fujimoto E, Kurobe A, Sugasawa N, Kitaichi T, Akaike M, Sata M, Matsumoto T, Kitagawa T.
  J Atheroscler Thromb. 2011;18(12):1080-9. Epub 2011 Oct 26.
  PMID: 22027560
• Interactions between CKD and MetS and the Development of CVD.
  Aihara K, Mogi M, Shibata R, Bishop-Bailey D, Ma XL.
  Cardiol Res Pract. 2011;2011:878065. doi: 10.4061/2011/878065. Epub 2011 May 16. No abstract available.
  PMID: 21629800
• Effect of low-dose (1 mg/day) pitavastatin on left ventricular diastolic function and albuminuria in patients with hyperlipidemia.
  Yagi S, Akaike M, Aihara K, Iwase T, Ishikawa K, Yoshida S, Sumitomo-Ueda Y, Kusunose K, Niki T, Yamaguchi K, Koshiba K, Taketani Y, Tomita N, Yamada H, Soeki T, Wakatsuki T, Matsumoto T, Sata M.
  Am J Cardiol. 2011 Jun 1;107(11):1644-9. doi: 10.1016/j.amjcard.2011.01.054. Epub 2011 Mar 31.
  PMID: 21458773
• Bosentan improves systemic sclerosis-related peripheral circulation insufficiency.
  Yagi S, Akaike M, Aihara K, Iwase T, Sumitomo-Ueda Y, Yoshida S, Matsumoto T, Sata M.
  Int J Cardiol. 2011 Mar 17;147(3):472-5. doi: 10.1016/j.ijcard.2011.01.025. Epub 2011 Feb 5. No abstract available.
  PMID: 21296436
• Plasma heparin cofactor II activity is inversely associated with left atrial volume and diastolic dysfunction in humans with cardiovascular risk factors.
  Ise T, Aihara K, Sumitomo-Ueda Y, Yoshida S, Ikeda Y, Yagi S, Iwase T, Yamada H, Akaike M, Sata M, Matsumoto T.
  Hypertens Res. 2011 Feb;34(2):225-31. doi: 10.1038/hr.2010.211. Epub 2010 Nov 25.
  PMID: 21107326
• Deferoxamine promotes angiogenesis via the activation of vascular endothelial cell function.
  Ikeda Y, Tajima S, Yoshida S, Yamano N, Kihira Y, Ishizawa K, Aihara K, Tomita S, Tsuchiya K, Tamaki T.
  Atherosclerosis. 2011 Apr;215(2):339-47. doi: 10.1016/j.atherosclerosis.2011.01.009. Epub 2011 Jan 21.
  PMID: 21315355

2010年の業績

• Transforming Growth Factor-β1 as a Common Target Molecule for Development of Cardiovascular Diseases, Renal Insufficiency and Metabolic Syndrome.
  Aihara K, Ikeda Y, Yagi S, Akaike M, Matsumoto T.
  Cardiol Res Pract. 2010 Dec 28;2011:175381. doi: 10.4061/2011/175381.
  PMID: 21234356
• Activation of peroxisome proliferator-activated receptor α in megakaryocytes reduces platelet-derived growth factor-BB in platelets.
  Hashizume S, Akaike M, Azuma H, Ishikawa K, Yoshida S, Sumitomo-Ueda Y, Yagi S, Ikeda Y, Iwase T, Aihara K, Abe M, Sata M, Matsumoto T.
  J Atheroscler Thromb. 2011;18(2):138-47. Epub 2010 Nov 2.
  PMID: 21060209
• Bosentan ameliorated exercise-induced pulmonary arterial hypertension complicated with systemic sclerosis.
  Yagi S, Akaike M, Iwase T, Kusunose K, Niki T, Yamaguchi K, Koshiba K, Yoshida S, Sumitomo-Ueda Y, Aihara K, Hirata Y, Dagvasumberel M, Taketani Y, Tomita N, Yamada H, Soeki T, Wakatsuki T, Matsumoto T, Sata M.
  Intern Med. 2010;49(21):2309-12. Epub 2010 Nov 1.
  PMID: 21048365
• High plasma aldosterone concentration is a novel risk factor of cognitive impairment in patients with hypertension.
  Yagi S, Akaike M, Aihara K, Iwase T, Yoshida S, Sumitomo-Ueda Y, Ikeda Y, Ishikawa K, Matsumoto T, Sata M.
  Hypertens Res. 2011 Jan;34(1):74-8. doi: 10.1038/hr.2010.179. Epub 2010 Sep 23.
  PMID: 20861841
• Dehydroepiandrosterone sulfate is inversely associated with sex-dependent diverse carotid atherosclerosis regardless of endothelial function.
  Yoshida S, Aihara K, Azuma H, Uemoto R, Sumitomo-Ueda Y, Yagi S, Ikeda Y, Iwase T, Nishio S, Kawano H, Miki J, Yamada H, Hirata Y, Akaike M, Sata M, Matsumoto T.
  Atherosclerosis. 2010 Sep;212(1):310-5. doi: 10.1016/j.atherosclerosis.2010.05.011. Epub 2010 Jun 2.
  PMID: 20627295
• Heparin cofactor II protects against angiotensin II-induced cardiac remodeling via attenuation of oxidative stress in mice.
  Sumitomo-Ueda Y, Aihara K, Ise T, Yoshida S, Ikeda Y, Uemoto R, Yagi S, Iwase T, Ishikawa K, Hirata Y, Akaike M, Sata M, Kato S, Matsumoto T.
  Hypertension. 2010 Sep;56(3):430-6. doi: 10.1161/HYPERTENSIONAHA.110.152207. Epub 2010 Jul 26. Erratum in: Hypertension. 2010 Nov;56(5):e168.
  PMID: 20660821
• Androgen receptor counteracts Doxorubicin-induced cardiotoxicity in male mice.
  Ikeda Y, Aihara K, Akaike M, Sato T, Ishikawa K, Ise T, Yagi S, Iwase T, Ueda Y, Yoshida S, Azuma H, Walsh K, Tamaki T, Kato S, Matsumoto T.
  Mol Endocrinol. 2010 Jul;24(7):1338-48. doi: 10.1210/me.2009-0402. Epub 2010 May 25.
  PMID: 20501642
• Heparin cofactor II attenuates vascular remodeling in humans and mice.
  Aihara K.
  Circ J. 2010 Aug;74(8):1518-23. Epub 2010 Jul 17. Review.
  PMID: 20671370
• Congenital ventricular aneurysm as an unexpected complication of monomorphic premature ventricular contractions.
  Yagi S, Akaike M, Fujimura M, Kimura T, Nishiuchi T, Iwase T, Aihara K, Yoshida S, Sumitomo-Ueda Y, Kusunose K, Niki T, Yamaguchi K, Koshiba K, Hirata Y, Dagvasumberel M, Taketani Y, Tomita N, Yamada H, Soeki T, Wakatsuki T, Matsumoto T, Sata M.
  Intern Med. 2010;49(10):907-12. Epub 2010 May 14.
  PMID: 20467175
• Endothelial nitric oxide synthase-independent protective action of statin against angiotensin II-induced atrial remodeling via reduced oxidant injury.
  Yagi S, Akaike M, Aihara K, Ishikawa K, Iwase T, Ikeda Y, Soeki T, Yoshida S, Sumitomo-Ueda Y, Matsumoto T, Sata M.
  Hypertension. 2010 Apr;55(4):918-23. doi: 10.1161/HYPERTENSIONAHA.109.146076. Epub 2010 Mar 1.
  PMID: 20194307
• Ezetimibe ameliorates metabolic disorders and microalbuminuria in patients with hypercholesterolemia.
  Yagi S, Akaike M, Aihara K, Iwase T, Ishikawa K, Yoshida S, Sumitomo-Ueda Y, Kusunose K, Niki T, Yamaguchi K, Koshiba K, Hirata Y, Dagvasumberel M, Taketani Y, Tomita N, Yamada H, Soeki T, Wakatsuki T, Matsumoto T, Sata M.
  J Atheroscler Thromb. 2010 Feb 26;17(2):173-80. Epub 2010 Feb 12.
  PMID: 20150722

2009年の業績

• Role of hypoxia-inducible factor 1alpha in T cells as a negative regulator in development of vascular remodeling
  Kurobe H, Urata M, Ueno M, Ueki M, Ono S, Izawa-Ishizawa Y, Fukuhara Y, Lei Y, Ripen AM, Kanbara T, Aihara K, Ishizawa K, Akaike M, Gonzalez FJ, Tamaki T, Takahama Y, Yoshizumi M, Kitagawa T, Tomita S.
  Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):210-7. doi: 10.1161/ATVBAHA.109.192666. Epub 2009 Dec 10.
  PMID: 20007912
• Inhibition of thrombin action ameliorates insulin resistance in type 2 diabetic db/db mice.
  Mihara M, Aihara K, Ikeda Y, Yoshida S, Kinouchi M, Kurahashi K, Fujinaka Y, Akaike M, Matsumoto T.
  Endocrinology. 2010 Feb;151(2):513-9. doi: 10.1210/en.2009-0661. Epub 2009 Dec 4.
  PMID: 19966184
• Decrease in plasma brain natriuretic peptide level in the early phase after the start of carvedilol therapy is a novel predictor of long-term outcome in patients with chronic heart failure.
  Fujimura M, Akaike M, Iwase T, Yoshida S, Sumitomo Y, Yagi S, Ikeda Y, Hashizume S, Aihara K, Nishiuchi T, Yasumura Y, Matsumoto T.
  Acta Cardiol. 2009 Oct;64(5):589-95.
  PMID: 20058503
• Heparin cofactor II as a novel vascular protective factor against atherosclerosis.
  Aihara K, Azuma H, Akaike M, Sata M, Matsumoto T.
  J Atheroscler Thromb. 2009 Oct;16(5):523-31. Epub 2009 Sep 3. Review.
  PMID: 19729870
• Heparin cofactor II is an independent protective factor against peripheral arterial disease in elderly subjects with cardiovascular risk factors.
  Aihara K, Azuma H, Akaike M, Kurobe H, Takamori N, Ikeda Y, Sumitomo Y, Yoshida S, Yagi S, Iwase T, Ishikawa K, Sata M, Kitagawa T, Matsumoto T.
  J Atheroscler Thromb. 2009 Apr;16(2):127-34. Epub 2009 Apr 30.
  PMID: 19403987
• Androgen-androgen receptor system protects against angiotensin II-induced vascular remodeling.
  Ikeda Y, Aihara K, Yoshida S, Sato T, Yagi S, Iwase T, Sumitomo Y, Ise T, Ishikawa K, Azuma H, Akaike M, Kato S, Matsumoto T.
  Endocrinology. 2009 Jun;150(6):2857-64. doi: 10.1210/en.2008-1254. Epub 2009 Feb 5.
  PMID: 19196803
• The Rab GTPase-activating protein AS160 as a common regulator of insulin- and Galphaq-mediated intracellular GLUT4 vesicle distribution.
  Yuasa T, Uchiyama K, Ogura Y, Kimura M, Teshigawara K, Hosaka T, Tanaka Y, Obata T, Sano H, Kishi K, Ebina Y.
  Endocr J. 2009;56(3):345-59. Epub 2009 Jan 9.
  PMID: 19139597

2008年の業績

• Infective endocarditis caused by lactobacillus.
  Yagi S, Akaike M, Fujimura M, Ise T, Yoshida S, Sumitomo Y, Ikeda Y, Iwase T, Aihara K, Azuma H, Kurushima A, Ichikawa Y, Kitagawa T, Kimura T, Nishiuchi T, Matsumoto T.
  Intern Med. 2008;47(12):1113-6. Epub 2008 Jun 16.
  PMID: 18552468
• IRS1-independent defects define major nodes of insulin resistance.
  Hoehn KL, Hohnen-Behrens C, Cederberg A, Wu LE, Turner N, Yuasa T, Ebina Y, James DE.
  Cell Metab. 2008 May;7(5):421-33. doi: 10.1016/j.cmet.2008.04.005.
  PMID: 18460333
• Pitavastatin, an HMG-CoA reductase inhibitor, exerts eNOS-independent protective actions against angiotensin II induced cardiovascular remodeling and renal insufficiency.
  Yagi S, Aihara K, Ikeda Y, Sumitomo Y, Yoshida S, Ise T, Iwase T, Ishikawa K, Azuma H, Akaike M, Matsumoto T.
  Circ Res. 2008 Jan 4;102(1):68-76. Epub 2007 Oct 25.
  PMID: 17967781

2007年の業績

• Improvement of cardiac diastolic function and prognosis after autologous peripheral blood stem cell transplantation in AL cardiac amyloidosis.
  Yagi S, Akaike M, Ozaki S, Moriya C, Takeuchi K, Hara T, Fujimura M, Sumitomo Y, Iwase T, Ikeda Y, Aihara K, Kimura T, Nishiuchi T, Abe M, Matsumoto T.
  Intern Med. 2007;46(20):1705-10. Epub 2007 Oct 15.
  PMID: 17938525
• Isolated high-molecular-weight kininogen deficiency: a novel frameshift mutation in exon 10.
  Shigekiyo T, Miyagi J, Shirakami A, Shibata H, Tsukai K, Aihara K.
  Blood. 2007 Jun 1;109(11):5062-3. No abstract available.
  PMID: 17522339
• Strain-dependent embryonic lethality and exaggerated vascular remodeling in heparin cofactor II-deficient mice.
  Aihara K, Azuma H, Akaike M, Ikeda Y, Sata M, Takamori N, Yagi S, Iwase T, Sumitomo Y, Kawano H, Yamada T, Fukuda T, Matsumoto T, Sekine K, Sato T, Nakamichi Y, Yamamoto Y, Yoshimura K, Watanabe T, Nakamura T, Oomizu A, Tsukada M, Hayashi H, Sudo T, Kato S, Matsumoto T.
  J Clin Invest. 2007 Jun;117(6):1514-26.
  PMID: 17549254

2006年の業績

• APS-mediated ubiquitination of the insulin receptor enhances its internalization, but does not induce its degradation.
  Kishi K, Mawatari K, Sakai-Wakamatsu K, Yuasa T, Wang M, Ogura-Sawa M, Nakaya Y, Hatakeyama S, Ebina Y.
  Endocr J. 2007 Feb;54(1):77-88. Epub 2006 Nov 14.
  PMID: 17102568
• Intra-vascular ultrasound findings of diffuse coronary atherosclerotic change in systemic lupus erythematosus with secondary antiphospholipid syndrome.
  Ikeda Y, Yagi S, Yamaguchi H, Fujimura M, Hashizume S, Aihara K, Akaike M, Azuma H, Matsumoto T.
  Circ J. 2006 Aug;70(8):1082-5.
  PMID: 16864946

2005年の業績

• Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenicity in mice.
  Aihara K, Azuma H, Akaike M, Ikeda Y, Yamashita M, Sudo T, Hayashi H, Yamada Y, Endoh F, Fujimura M, Yoshida T, Yamaguchi H, Hashizume S, Kato M, Yoshimura K, Yamamoto Y, Kato S, Matsumoto T.
  J Biol Chem. 2004 Aug 20;279(34):35798-802. Epub 2004 Jun 17.
  PMID: 15205460
• Androgen receptor gene knockout male mice exhibit impaired cardiac growth and exacerbation of angiotensin II-induced cardiac fibrosis.
  Ikeda Y, Aihara K, Sato T, Akaike M, Yoshizumi M, Suzaki Y, Izawa Y, Fujimura M, Hashizume S, Kato M, Yagi S, Tamaki T, Kawano H, Matsumoto T, Azuma H, Kato S, Matsumoto T.
  J Biol Chem. 2005 Aug 19;280(33):29661-6. Epub 2005 Jun 16.
  PMID: 15961403
• Aspirin inhibits thrombin action on endothelial cells via up-regulation of aminopeptidase N/CD13 expression.
  Kato M, Azuma H, Akaike M, Iuchi T, Aihara K, Ikeda Y, Fujimura M, Yoshida T, Yamaguchi H, Hashizume S, Matsumoto T.
  Atherosclerosis. 2005 Nov;183(1):49-55. Epub 2005 Apr 15.
  PMID: 16216591
• Vascular smooth muscle cell proliferation is dependent upon upregulation of mitochondrial transcription factor A (mtTFA) expression in injured rat carotid artery.
  Yoshida T, Azuma H, Aihara K, Fujimura M, Akaike M, Mitsui T, Matsumoto T.
  Atherosclerosis. 2005 Jan;178(1):39-47.
  PMID: 15585199

2004年の業績

• Platelet-derived growth factor stimulates glucose transport in skeletal muscles of transgenic mice specifically expressing platelet-derived growth factor receptor in the muscle, but it does not affect blood glucose levels.
  Yuasa T, Kakuhata R, Kishi K, Obata T, Shinohara Y, Bando Y, Izumi K, Kajiura F, Matsumoto M, Ebina Y.
  Diabetes. 2004 Nov;53(11):2776-86. Erratum in: Diabetes. 2005 Jan;54(1):296.
  PMID: 15504957
• Heparin cofactor II is a novel protective factor against carotid atherosclerosis in elderly individuals.
  Aihara K, Azuma H, Takamori N, Kanagawa Y, Akaike M, Fujimura M, Yoshida T, Hashizume S, Kato M, Yamaguchi H, Kato S, Ikeda Y, Arase T, Kondo A, Matsumoto T.
  Circulation. 2004 Jun 8;109(22):2761-5. Epub 2004 May 17.
  PMID: 15148272
• K(ATP) channel knockout mice crossbred with transgenic mice expressing a dominant-negative form of human insulin receptor have glucose intolerance but not diabetes.
  Kanezaki Y, Obata T, Matsushima R, Minami A, Yuasa T, Kishi K, Bando Y, Uehara H, Izumi K, Mitani T, Matsumoto M, Takeshita Y, Nakaya Y, Matsumoto T, Ebina Y.
  Endocr J. 2004 Apr;51(2):133-44.
  PMID: 15118262
• Brain masculinization requires androgen receptor function.
  Sato T, Matsumoto T, Kawano H, Watanabe T, Uematsu Y, Sekine K, Fukuda T, Aihara K, Krust A, Yamada T, Nakamichi Y, Yamamoto Y, Nakamura T, Yoshimura K, Yoshizawa T, Metzger D, Chambon P, Kato S.
  Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1673-8. Epub 2004 Jan 27.
  PMID: 14747651
• High plasma heparin cofactor II activity is associated with reduced incidence of in-stent restenosis after percutaneous coronary intervention.
  Takamori N, Azuma H, Kato M, Hashizume S, Aihara K, Akaike M, Tamura K, Matsumoto T.
  Circulation. 2004 Feb 3;109(4):481-6. Epub 2004 Jan 26.
  PMID: 14744972

2003年の業績

• Suppressive function of androgen receptor in bone resorption.
  Kawano H, Sato T, Yamada T, Matsumoto T, Sekine K, Watanabe T, Nakamura T, Fukuda T, Yoshimura K, Yoshizawa T, Aihara K, Yamamoto Y, Nakamichi Y, Metzger D, Chambon P, Nakamura K, Kawaguchi H, Kato S.
  Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9416-21. Epub 2003 Jul 18.
  PMID: 12872002
• Chondromodulin I is a bone remodeling factor.
  Nakamichi Y, Shukunami C, Yamada T, Aihara K, Kawano H, Sato T, Nishizaki Y, Yamamoto Y, Shindo M, Yoshimura K, Nakamura T, Takahashi N, Kawaguchi H, Hiraki Y, Kato S.
  Mol Cell Biol. 2003 Jan;23(2):636-44.
  PMID: 12509461

2002年の業績

• Effect of aspirin treatment on serum concentrations of lipoprotein(a) in patients with atherosclerotic diseases.
  Akaike M, Azuma H, Kagawa A, Matsumoto K, Hayashi I, Tamura K, Nishiuchi T, Iuchi T, Takamori N, Aihara K, Yoshida T, Kanagawa Y, Matsumoto T.
  Clin Chem. 2002 Sep;48(9):1454-9.
  PMID: 12194922