The role of long non-cording RNA in pathological mechanism of heart failure.

• Project/Area Number: 25461114
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kumamoto University
• Principal Investigator: MIYATA KEISHI 熊本大学, 生命科学研究部, 特任准教授 (50398228)
• Co-Investigator(Kenkyū-buntansha): 荒木 喜美 熊本大学, 学内共同利用施設等, 教授 (90211705)
• 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: non-coding RNA / non-cording RNA / 心不全

Outline of Final Research Achievements

We found that embryonic cardiac specific expressed-clones among unknown long non-coding RNA (lnc RNA) clones using gene trap methods. In one clone of them, the trap vector was inserted into the intron site of lnc RNA AK141659 gene. We elucidated that its clone’s homozygous mice were AK141659 KO mice. AK141659 KO mice did not exhibit significant differences in cardiac morphology and function compared with wild-type mice. To assess the role of AK141659 in pathological mechanism of heart failure, we operated transverse aorta constriction model (TAC) using AK141659 KO mice and analyzed the cardiac function of them.

Academic Significance and Societal Importance of the Research Achievements

マウスの個体を用いたlncRNAと心疾患の病態形成分子機構に関する解析は現在数少なく、この研究方法および結果は非常に貴重な成果になると期待される。本研究により細胞質に存在するlncRNAの新たな作用機構の解明だけでなく、種々の遺伝子改変マウスを用いることで生体の心臓における分子機構が明らかになると期待される。さらに、この心不全病態形成における細胞質lncRNAの基盤研究が、トランスレーショナルリサーチとして、心不全の予防医学に向けた新規治療法開発へと期待される。

Research Products

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• [Journal Article] Role of endothelial cell-derived angptl2 in vascular inflammation leading to endothelial dysfunction and atherosclerosis progression. (2014)
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• [Journal Article] The angiotensin II AT1 receptor-associated protein Arap1 is involved in sepsis-induced hypotension. (2013)
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• [Journal Article] Angiopoietin-like protein 2 is a potent hemangiogenic and lymphangiogenic factor in corneal inflammation. (2013)
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• [Journal Article] A molecular clock regulates angiopoietin-like protein 2 expression. (2013)
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• [Journal Article] Perivascular adipose tissue-secreted angiopoietin-like protein2 (Angptl2) accelerates neointimal hyperplasia after endovascular injury. (2013)
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  • Journal Title: Journal of Molecular and Cellular Cardiology Volume: 57 Pages: 1-12
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• [Presentation] 病的血管リモデリングにおける血管周囲脂肪組織由来Angptl2の役割 (2015)
  • Author(s): 宮田敬士
  • Organizer: 第23回日本血管生物医学会学術集会
  • Place of Presentation: 兵庫県神戸市
• [Presentation] Lack of Angiopoietin-like Protein 2 (Angptl2) Prevents Heart Failure in Murine Left Ventricular Pressure-overload Model (2014)
  • Author(s): Keishi Miyata、Zhe Tian、Eiji Horio、Hirokazu Tadume、Yuichi Oike
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京・東京国際フォーラム