Analysis of mechanisms of overexpression of angiotensin converting enzyme and heart failure in transgenic mice of miRNAs

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460506
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Chubu University
• Principal Investigator: IWAMOTO Takashi 中部大学, 生命健康科学部, 教授 (60223426)
• Co-Investigator(Kenkyū-buntansha): ICHIHARA Masatoshi 中部大学, 生命健康科学部, 教授 (00314013) ; NODA Akiko 中部大学, 臨床検査技術教育・実習センター, 教授 (80252287)
• Co-Investigator(Renkei-kenkyūsha): OUCHI Yasuo 千葉大学, 大学院医学系研究科, 助教 (70553858) ; UEYAMA Tomomi 京都府立医科大学, 医学系研究科, 講師 (80379388)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: マイクロRNA / 拡張型心筋症 / アンジオテンシン変換酵素 / ヘキソキナーゼ２ / MAS1

Outline of Final Research Achievements

Dilated cardiomyopathy is one of the intractable diseases. microRNAs are small molecules, which were discovered around two decades ago, and have turned out to be involved in many human diseases. We generated the transgenic mice that expressed miR-143/145 in the heart muscles, and found that they died due to the human-like dilated cardiomyopathy.
The expression of angiotensin converting enzyme (ACE) increased in their hearts and ACE inhibitor significantly improved the condition of the mice. In addition, while ACE2 expression was also increased, the MAS1 receptor was clearly downregulated. These data imply that the dysregulation of key molecules of angiotensin metabolism might be involved in the pathology of these mice. Furthermore, we found that one glycolysis enzyme, hexokinase 2(HK2), was dramatically decreased in the hearts of the mice, and the expression of key molecules of autophagy was disturbed, suggesting the disorder of autophagy might be involved in this pathology.

Free Research Field

分子生物学