Aldolase promotes the development of cardiac hypertrophy by targeting AMPK signaling
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China)
Highlights: • Aldolase A (AldoA) is overexpressed in hypertrophic hearts. • AldoA promotes cardiomyocyte hypertrophy in vitro. • AldoA knockdown represses cardiac hypertrophy in vivo. • AMPK is critically involved in AldoA function in cardiac hypertrophy. Metabolic dysfunction is a hallmark of cardiac hypertrophy and heart failure. During cardiac failure, the metabolism of cardiomyocyte switches from fatty acid oxidation to glycolysis. However, the roles of key metabolic enzymes in cardiac hypertrophy are not understood fully. Here in the present work, we identified Aldolase A (AldoA) as a core regulator of cardiac hypertrophy. The mRNA and protein levels of AldoA were significantly up-regulated in transverse aortic constriction (TAC)- and isoproterenol (ISO)-induced hypertrophic mouse hearts. Overexpression of AldoA in cardiomyocytes promoted ISO-induced cardiomyocyte hypertrophy, whereas AldoA knockdown repressed cardiomyocyte hypertrophy. In addition, adeno-associated virus 9 (AAV9)-mediated in vivo knockdown of AldoA in the hearts rescued ISO-induced decrease in cardiac ejection fraction and fractional shortening and repressed cardiac hypertrophy. Mechanism study revealed that AldoA repressed the activation of AMP-dependent protein kinase (AMPK) signaling in a liver kinase B1 (LKB1)-dependent and AMP-independent manner. Inactivation of AMPK is a core mechanism underlying AldoA-mediated promotion of ISO-induced cardiomyocyte hypertrophy. By contrast, activation of AMPK with metformin and AICAR blocked AldoA function during cardiomyocyte hypertrophy. In summary, our data support the notion that AldoA-AMPK axis is a core regulatory signaling sensing energetic status and participates in cardiac hypertrophy.
- OSTI ID:
- 23082665
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 370; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
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