Key result
In vivo delivery of small interfering RNA targeting MEF2C attenuated load-induced left ventricular hypertrophy, interstitial fibrosis, and ANP upregulation in aortic banded mice.
Why the study?
Does MEF2C silencing attenuate load-induced left ventricular hypertrophy in mice?
Does MEF2C silencing attenuate load-induced left ventricular hypertrophy in mice?
p-value: p=<0.05
MEF2C depletion attenuates hypertrophic responses to mechanical stress in a mouse model, highlighting its potential as a therapeutic target for cardiac hypertrophy and failure.
MEF2C silencing attenuates load-induced LVH in mice; hypothesis-generating for therapeutic targeting in human cardiac hypertrophy.
BACKGROUND: The activation of the members of the myocyte enhancer factor-2 family (MEF2A, B, C and D) of transcription factors promotes cardiac hypertrophy and failure. However, the role of its individual components in the pathogenesis of cardiac hypertrophy remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated whether MEF2C plays a role in mediating the left ventricular hypertrophy by pressure overload in mice. The knockdown of myocardial MEF2C induced by specific small interfering RNA (siRNA) has been shown to attenuate hypertrophy, interstitial fibrosis and the rise of ANP levels in aortic banded mice. We detected that the depletion of MEF2C also results in lowered levels of both PGC-1alpha and mitochondrial DNA in the overloaded left ventricle, associated with enhanced AMP:ATP ratio. Additionally, MEF2C depletion was accompanied by defective activation of S6K in response to pressure overload. Treatment with the amino acid leucine stimulated S6K and suppressed the attenuation of left ventricular hypertrophy and fibrosis in the aforementioned aortic banded mice. CONCLUSION/SIGNIFICANCE: These findings represent new evidences that MEF2C depletion attenuates the hypertrophic responses to mechanical stress and highlight the potential of MEF2C to be a target for new therapies to cardiac hypertrophy and failure.
No takes yet. Share an insight, caveat, or question.
Pereira et al. (2009) studied Left ventricular hypertrophy. siMEF2C (small interfering RNA targeted to MEF2C) vs. siGFP (Green Fluorescent Protein siRNA) was evaluated on Left ventricular hypertrophy (assessed by left ventricular wall thickness and mass/body mass ratio) (p=<0.05). In vivo delivery of small interfering RNA targeting MEF2C attenuated load-induced left ventricular hypertrophy, interstitial fibrosis, and ANP upregulation in aortic banded mice.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: