Epigenetics of renin-angiotensin-aldosterone in salt-sensitive hypertension

• Project/Area Number: 25461244
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kanazawa University
• Principal Investigator: Takeda Yoshiyu 金沢大学, 大学病院, 特任教授 (90242544)
• Research Collaborator: TAKEDA Yoshimichi ; WANG Fen
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: アンジオテンシノーゲン / エピゲノム / 高血圧 / 食塩感受性 / アルドステロン / グルココルチコイド / メチル化 / DNAメチル化 / 高食塩食 / 心血管系 / 食塩感受性高血圧 / エピジェネティクス / プロモーター / 転写活性

Outline of Final Research Achievements

Salt-sensitive hypertension is the most popular disease in Japan. CYP11B2 gene expression was elevated and methylation ratio was decreased in human adrenal glomerulosa. High salt diet increased vascular CYP11B2 mRNA expression and angiotensinogen mRNA levels in the heart in salt-sensitive hypertensive rats. Hypomethylation status of angiotensinogen gene was seen in the heart. High salt diet may influence methylation status of genes of renin-angiotensin-aldosterone system and cause hypertension.

Research Products

• [Journal Article] Dynamic regulation og angiotensinogen gene by DNA methylation, which is influenced by various stimuli experienced in daily life (2015)
  • Author(s): 1)Demura M, Demura Y, Takeda Y, Saijoh K
  • Journal Title: Hypertension Reserach Volume: 38 Issue: 8 Pages: 619-27
  • DOI: 10.1038/hr.2015.42
  • Peer Reviewed / Open Access
• [Journal Article] Dynamic CCAAT/Enhancer Binding Protein–Associated Changes of DNA Methylation in the Angiotensinogen Gene (2014)
  • Author(s): Fen Wang, Masashi Demura, Yuan Cheng, Aoshuang Zhu, Shigehiro Karashima, Takashi Yoneda, Yoshiki Demura, Yuji Maeda, Mikio Namiki, Katsuhiko Ono, Yasuhiro Nakamura, Hironobu Sasano, Tadayuki Akagi, Masakazu Yamagishi, Kiyofumi Saijoh, Yoshiyu Takeda
  • Journal Title: Hypertension. Volume: 63(2) Issue: 2 Pages: 281-288
  • DOI: 10.1161/hypertensionaha.113.02303
  • Peer Reviewed / Open Access
• [Presentation] Epigenetic Control of CYP11B2 Gene by High Salt Diet (2016)
  • Author(s): Yoshiyu Takeda, Yoshimichi Takeda, Takashi Yoneda, Mitsuhiro Kometani, Shigehiro Karashima, Atsushi Hashimoto
  • Organizer: ENDO2016
  • Place of Presentation: Boston（USA)
  • Year and Date: 2016-04-01
  • Int'l Joint Research
• [Presentation] 肥大心におけるアンジオテンシノーゲン遺伝子のエピジェネティック制御 (2015)
  • Author(s): 武田仁裕, 米田隆, 米谷充弘, 臼倉幹哉, 若林祐介, 奥田理香, 出村昌史, 山岸正和, 笹野公伸, 織田展成, 武田仁勇
  • Organizer: 第38回日本高血圧学会総会
  • Place of Presentation: 愛媛県県民文化会館(松山,愛媛県)
  • Year and Date: 2015-10-09
• [Presentation] 食塩感受性高血圧におけるレニン-アンジオテンシン-アルドステロン系のエピジェネティクス (2015)
  • Author(s): 武田仁勇, 出村昌史, 米田隆, 武田仁裕, 米谷充弘
  • Organizer: 第38回日本高血圧学会総会
  • Place of Presentation: 愛媛県県民文化会館（松山,愛媛県)
  • Year and Date: 2015-10-09
  • Invited
• [Presentation] HIGH SALT DIET INFLUENCES ANGIOTENSINOGEN GENE EPIGENESIS IN SALTSENSITIVE HYPERTENSIVE RATS (2015)
  • Author(s): Y. Takeda, T. Yoneda, M. Kometani, S. Karashima, Y. Takeda Jr, D. Aono.
  • Organizer: ESH
  • Place of Presentation: Milano（Itaria)
  • Year and Date: 2015-06-12
  • Int'l Joint Research
• [Presentation] アルドステロンはコルチゾール以上にヒト内臓脂肪アンジオテンシノーゲン転写を刺激する (2015)
  • Author(s): 出村昌史, 王芬, 唐島成宙, 米田隆, 武田仁勇, 西條清史
  • Organizer: 第88回日本内分泌学会学術総会
  • Place of Presentation: ホテルニュー大谷東京(東京)
  • Year and Date: 2015-04-23
• [Presentation] Epigenetic control of renin-angiotensin-aldosterone system in hypertrophic heart (2014)
  • Author(s): Yoshiyu Takeda, Takashi Yoneda, Fen Wang, Mitsuhiro Kometani
  • Organizer: European Congress of Endocrinology
  • Place of Presentation: Hala Stuleccia (Wroctaw, Poland)
  • Year and Date: 2014-05-03 – 2014-05-07
• [Presentation] インターロイキン6のCCAAT/enhancer binding protein(C/EBP)領域を介するアンジオテンシノーゲン遺伝子のメチレーション制御 (2014)
  • Author(s): 王芬，出村昌史，程媛，米田隆，米谷充弘，武田仁勇
  • Organizer: 日本内分泌学会
  • Place of Presentation: 福岡国際会議場(福岡)
  • Year and Date: 2014-04-26 – 2014-04-28
• [Presentation] インターロイキン6のCCAAT/enhancer binding protein (C/EBP)領域を介するアンジオテンシノーゲン遺伝子のメチレーション制御 (2014)
  • Author(s): 王芬、出村昌史、米谷光弘、米田隆、武田仁勇
  • Organizer: 第87回日本内分泌学会
  • Place of Presentation: 博多
• [Remarks] 金沢大学大学院循環器病態内科学
  • URL: http://intmed2.w3.kanazawa-u.ac.jp/
• [Remarks] 金沢大学大学院医学系研究科臓器機能制御学
  • URL: http://intmed2.w3.kanazawa-u.ac.jp