Myocardium-Specific Deletion of Rac1 Causes Ventricular Noncompaction and Outflow Tract Defects.

BACKGROUND

Left ventricular noncompaction (LVNC) is a cardiomyopathy that can lead to arrhythmias, embolic events and heart failure. Despite our current knowledge of cardiac development, the mechanisms underlying noncompaction of the ventricular myocardium are still poorly understood. The small GTPase acts as a crucial regulator of numerous developmental events. The present study aimed to investigate the cardiomyocyte specific role of in embryonic heart development.

METHODS AND RESULTS

The transgenic mice were crossed with mice to generate mice with a cardiomyocyte specific deletion of () during heart development. Embryonic hearts at E12.5-E18.5 were collected for histological analysis. Overall, hearts displayed a bifid apex, along with hypertrabeculation and a thin compact myocardium. hearts also exhibited ventricular septal defects (VSDs) and double outlet right ventricle (DORV) or overriding aorta. Cardiomyocytes had a rounded morphology and were highly disorganized, and the myocardial expression of Scrib, a planar cell polarity protein, was reduced in hearts. In addition, cell proliferation rate was significantly decreased in the ventricular myocardium at E9.5.

CONCLUSIONS

deficiency in the myocardium impairs cardiomyocyte elongation and organization, and proliferative growth of the heart. A spectrum of CHDs arises in hearts, implicating signaling in the ventricular myocardium as a crucial regulator of OFT alignment, along with compact myocardium growth and development.