Vascular endothelial Non-coding RNA modulates molecular and pathological interaction of hypertension with Alzheimer disease

• Project/Area Number: 17H04155
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Osaka University (2019-2021); National Cardiovascular Center Research Institute (2017-2018)
• Principal Investigator: Hayashi Shinichiro 大阪大学, 医学系研究科, 特任准教授 (20396740)
• Co-Investigator(Kenkyū-buntansha): 伊藤 義晃 東京医科歯科大学, 統合研究機構, 助教 (50511044) ; 里 直行 国立研究開発法人国立長寿医療研究センター, 認知症先進医療開発センター, 副センター長 (70372612)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
• Keywords: 血管内皮 / Non-coding RNA / 高血圧 / 認知症 / Non-Coding RNA

Outline of Final Research Achievements

The cause and progression of Alzheimer disease (AD) still remain uncertain, while pathological interaction of AD with lifestyle diseases, including hypertension and diabetes, has been suggested in clinical settings.
Our present findings indicate that several vascular endothelial specific Non-coding RNA might be responsible for the molecular and pathological interaction of AD with hypertension, and thereby will be new therapeutic targets against AD as well as lifestyle diseases.

Academic Significance and Societal Importance of the Research Achievements

認知症は、生活習慣病とともに増加傾向にあり、社会国民に重大な影響を与えている。そのため、新しい治療方法や早期診断方法の開発は健康長寿社会の実現ために急務となっている。
本研究で明らかになった、血管内皮細胞由来のNon-Coding RNA（ncRNA）を手がかりに、認知症の分子治療薬や早期病態診断方法の開発、さらには生活習慣病、脳心血管病、癌などの新しい治療薬開発につながることが期待される。
選定されたncRNAは、細胞内リサイクリングシステムに関与するものもあり、新たな細胞機能制御のメカニズム発見も期待される。

Research Products

• [Journal Article] Impact of Percutaneous Transluminal Renal Angioplasty on Autonomic Nervous System and Natriuresis in Hypertensive Patients With Renal Artery Stenosis (2022)
  • Author(s): Iwashima Y、Hayashi S他
  • Journal Title: Journal of the American Heart Association Volume: 11 Issue: 6
  • DOI: 10.1161/jaha.121.023655
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of Percutaneous Transluminal Renal Angioplasty on Left Ventricular Mass and Its Relationship to Cardiovascular Outcome in Hypertensive Patients With Renal Artery Stenosis (2021)
  • Author(s): Iwashima Y、Hayashi S他
  • Journal Title: Journal of Hypertension Volume: 39
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Associations between arterial stiffness indices and chronic kidney disease categories in essential hypertensive patients (2020)
  • Author(s): Kusunoki H、Hayashi S他
  • Journal Title: American Journal of Hypertension Volume: 34 Issue: 5 Pages: 484
  • DOI: 10.1093/ajh/hpaa163
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Impact of Percutaneous Revascularization on Left Ventricular Mass and Its Relationship to Outcome in Hypertensive Patients with Renal Artery Stenosis (2020)
  • Author(s): Iwashima Yoshio、Fukuda Tetsuya、Horio Takeshi、Kusunoki Hiroshi、Hayashi Shin-ichiro、Kamide Kei、Kawano Yuhei、Ishimitsu Toshihiko、Yoshihara Fumiki
  • Journal Title: American Journal of Hypertension Volume: 33 Issue: 6 Pages: 570
  • DOI: 10.1093/ajh/hpaa036
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Insight into the Role of Angiopoietins in Ageing-Associated Diseases (2020)
  • Author(s): Hayashi Shin-ichiro他
  • Journal Title: Cells Volume: 9 Issue: 12 Pages: 2636-2636
  • DOI: 10.3390/cells9122636
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Association between circadian hemodynamic characteristics and target organ damage in patients with essential hypertension (2019)
  • Author(s): Kusunoki Hiroshi、Iwashima Yoshio、Kawano Yuhei、Hayashi Shin-ichiro、Kishida Masatsugu、Horio Takeshi、Shinmura Ken、Yoshihara Fumiki
  • Journal Title: American Journal of Hypertension Volume: 32 Issue: 8 Pages: 742
  • DOI: 10.1093/ajh/hpz088
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Hypertension Interacts With Alzheimer'S Disease via Autophagy-related Phenotypic Changes in Vascular Endothelial Cells (2019)
  • Author(s): Hayashi Shin-ichiro他
  • Journal Title: STROKE Volume: 50 supple1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Circadian hemodynamic characteristics in hypertensive patients with primary aldosteronism (2018)
  • Author(s): Kusunoki Hiroshi、Iwashima Yoshio、Kawano Yuhei、Hayashi Shin-ichiro、Kishida Masatsugu、Horio Takeshi、Shinmura Ken、Yoshihara Fumiki
  • Journal Title: Journal of Hypertension Volume: 36 Issue: 11 Pages: 2260
  • DOI: 10.1097/hjh.0000000000001800
  • Peer Reviewed
• [Journal Article] Association between renal function and outcomes after percutaneous transluminal renal angioplasty in hypertensive patients with renal artery stenosis (2018)
  • Author(s): Iwashima Yoshio、Fukuda Tetsuya、Horio Takeshi、Hayashi Shin-ichiro、Kusunoki Hiroshi、Kishida Masatsugu、Nakamura Satoko、Kamide Kei、Kawano Yuhei、Yoshihara Fumiki
  • Journal Title: Journal of Hypertension Volume: 36 Issue: 1 Pages: 126
  • DOI: 10.1097/hjh.0000000000001499
  • Peer Reviewed / Open Access
• [Journal Article] Effects of Percutaneous Transluminal Renal Angioplasty on Office and Home Blood Pressure and Home Blood Pressure Variability in Hypertensive Patients with Renal Artery Stenosis (2017)
  • Author(s): Iwashima Y, Hayashi S 他
  • Journal Title: HYPERTENSION Volume: 69 Issue: 1 Pages: 109
  • DOI: 10.1161/hypertensionaha.116.08124
  • Peer Reviewed / Open Access
• [Journal Article] Effective uric acid-lowering treatment for hypertensive patients with hyperuricemia (2017)
  • Author(s): Ohta Yuko、Ishizuka Azusa、Arima Hisatomi、Hayashi Shinichiro、Iwashima Yoshio、Kishida Masatsugu、Yoshihara Fumiki、Nakamura Satoko、Kawano Yuhei
  • Journal Title: Hypertension Research Volume: 40 Issue: 3 Pages: 259
  • DOI: 10.1038/hr.2016.139
  • URL: https://pure.teikyo.jp/en/publications/7ff0fac9-e3e7-4341-925e-5297708cc42d
  • Peer Reviewed / Open Access
• [Presentation] 高血圧と血管内皮のオートファジー制御 (2021)
  • Author(s): 林真一郎他
  • Organizer: 第51回腎臓学会西部学術集会
• [Presentation] Impact of percutaneous transluminal renal angioplasty of left ventricular mass and its relationship to cardiovascular outcome in hypertensive patients with renal artery stenosis (2021)
  • Author(s): Iwashima Y, Hayashi S他
  • Organizer: ESH-ISH 2021
  • Int'l Joint Research
• [Presentation] Hypertension Interacts With Alzheimer'S Disease via Autophagy-related Phenotypic Changes in Vascular Endothelial Cells (2019)
  • Author(s): Hayashi S他
  • Organizer: International Stroke Conference
  • Int'l Joint Research
• [Presentation] Hemodynamic Characteristics in Essential Hypertension Patients with Target Organ Damage (2019)
  • Author(s): 楠博、岩嶋義雄、林真一郎他
  • Organizer: 第42回日本高血圧学会総会
• [Presentation] Phosphodiesterase-3 inhibitor regulates endothelial autophagy and re-endothelialization in experimental models of a first-generation mTOR inhibitor eluting-stent. (2018)
  • Author(s): Hayashi S他
  • Organizer: American Heart Association Scientific Sessions 2018
  • Int'l Joint Research
• [Presentation] Hemodynamic characteristics in essential hypertensive patients with target organ damage. (2018)
  • Author(s): Iwashima Y, Hayashi S他
  • Organizer: American Heart Association Scientific Sessions 2018
  • Int'l Joint Research
• [Presentation] Hypertension interacts with Alzheimer’s disease via autophagy-related phenotypic changes in vascular endothelial cells. (2018)
  • Author(s): Hayashi S他
  • Organizer: International Stroke Conference 2019
  • Int'l Joint Research
• [Presentation] 脳心血管疾患合併患者の透析実施時の血圧管理. シンポジウム、第7回臨床高血圧フォーラム (2018)
  • Author(s): 吉原史樹、林真一郎他
  • Organizer: 第7回臨床高血圧フォーラム, 2018
• [Presentation] Androgen receptor associated molecule, ARA70, modulates postnatal neovascularization. (2017)
  • Author(s): Hayashi S, Ito H 他
  • Organizer: American Heart Association Scientific Sessions 2017
  • Int'l Joint Research
• [Presentation] Hypertension interacts with Alzheimer’s disease via autophagy-related phenotypic changes of endothelial cells. (2017)
  • Author(s): Hayashi S.
  • Organizer: Veterans Affairs Palo Alto Health Care System
  • Invited
• [Presentation] アンドロゲンレセプター関連分子ARA70の血管内皮における働き (2017)
  • Author(s): 林真一郎, 伊藤義晃 他
  • Organizer: 第40回日本高血圧学会総会
  • Invited
• [Presentation] 動脈硬化性の腎血管性高血圧患者における腎機能と経皮的腎血管形成術（PTRA）後の心血管・腎予後との関連 (2017)
  • Author(s): 岩嶋義雄、林真一郎 他
  • Organizer: 第40回日本高血圧学会総会
• [Presentation] 血圧日内変動性と腎障害との関連：上腕血圧と中心血圧の同時測定による検討 (2017)
  • Author(s): 楠博、林真一郎 他
  • Organizer: 第40回日本高血圧学会総会
• [Presentation] 上腕血圧と中心血圧の日内変動性と腎障害との関連 (2017)
  • Author(s): 楠博、林真一郎 他
  • Organizer: 第60回日本腎臓学会学術総会