Application of genome editing and development-associated APJ ligand for exploring novel therapeutic candidates for heart failure

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15304
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Akita University
• Principal Investigator: Keiji Kuba 秋田大学, 医学(系)研究科(研究院), 教授 (10451915)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: ELABELA / Apelin / CRISPR/Cas9 / heart failure

Outline of Final Research Achievements

We investigated the role of APJ ligand ELABELA and novel heart failure gene candidates in controlling heart functions by utilizing CRISPR/Cas9 genome editing in ES cells and functional analyses of G0 mice. ELA peptide treatment improved heart function and hypertrophy and reduced cardiac fibrosis in mice with TAC pressure overload. Mechanistically, ELA down-regulated transcription of ACE and thereby negatively regulates renin-angiotensin system. We also generated several new lines of mutant G0 mice for heart failure gene candidates and analyzed heart functions. Furthermore, we crossed the G0 mice for F1 and F2 generations and analyzed heart functions, leading to confirmation of 5 heart failure genes. The candidate approach with rapid generation and functional screening is efficient and useful in identifying novel heart failure genes and might contribute to boosting up cardiovascular research.

Free Research Field

分子心臓学