AAV9-mediated CDC14A RNA interference increased ejection fraction by 17% (from 28.3% to 45.1%, p<0.0001) and improved cardiac structure in a mouse model of Dilated Cardiomyopathy.
Does CDC14A loss of function improve cardiac structure and function in a mouse model of Dilated Cardiomyopathy?
CDC14A loss of function improves cardiac structure and function in a mouse model of Dilated Cardiomyopathy, identifying it as a potential novel therapeutic target for heart failure with reduced ejection fraction.
Effect estimate: 17% increase in ejection fraction
Absolute Event Rate: 45.1% vs 28.3%
p-value: p=<0.0001
What is new: A function is identified for the first time for the protein phosphatase CDC14A in the heart, regulation of cardiomyocyte morphology and overall cardiac geometry in pathological cardiac remodeling.The lysine methyltransferase KMT5A is shown to mediate the effects of CDC14A in the adult cardiomyocyte by regulating H4K20 mono-methylation, such that reduced KMT5A expression promotes a phenotype resembling Dilated Cardiomyopathy.H4K20me1 epigenomic modification is identified as a regulator of cardiac structure and function.Clinical implications: CDC14A loss of function experimentation in vivo , resulting in improved cardiac structure and function in a mouse model of Dilated Cardiomyopathy, suggests that CDC14A is a novel therapeutic target for heart failure with reduced ejection fraction.
Li et al. (Tue,) conducted a other in Wild-type C57BL/6NJ mice and FVB/N mice with Tpm1 E54K transgene model of Dilated Cardiomyopathy. Adeno-associated virus (AAV)-mediated cardiomyocyte-specific RNA interference targeting CDC14A or KMT5A vs. AAV-mediated expression of control shRNA (shControl) was evaluated on Cardiac structure and function measured by echocardiography (fractional shortening, ejection fraction, left ventricular volumes and wall thickness) and morphological analysis (cardiomyocyte width:length ratio, heart weight indices) (17% increase in ejection fraction, p=<0.0001). AAV9-mediated CDC14A RNA interference increased ejection fraction by 17% (from 28.3% to 45.1%, p<0.0001) and improved cardiac structure in a mouse model of Dilated Cardiomyopathy.