| Budget Amount *help |
¥42,250,000 (Direct Cost: ¥32,500,000、Indirect Cost: ¥9,750,000)
Fiscal Year 2023: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2022: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2021: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
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| Outline of Final Research Achievements |
The molecular mechanisms underlying heart failure development caused by the alternations of cardiac adaptive remodeling are not fully elucidated. In this study, we showed that alternations in control of cardiac mitochondrial quantity and quality cause pathologic cardiomyocyte hypertrophy and cardiac fibrosis and subsequent development of heart failure. Furthermore, we found that aging and pressure overload decrease the expression of a novel long non-coding RNA Caren in cardiomyocytes. Decreased Caren expression accelerates decline in mitochondrial biogenesis and activation of DNA damage responses in cardiomyocytes and leads to development and progression of heart failure, suggesting that Caren exhibits the cardioprotective effects. In addition, we demonstrated that adeno-associated virus (AAV)-mediated gene delivery of Caren to cardiomyocytes could be a novel therapeutic strategy for heart failure.
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