Key result
Cardiac-specific inhibition of Rho family proteins in mice led to progressive atrioventricular block and atrial arrhythmias, while preserving ventricular contractile function.
Why the study?
Does cardiac-specific inhibition of Rho family proteins affect atrioventricular conduction and ventricular function in mice?
Does cardiac-specific inhibition of Rho family proteins affect atrioventricular conduction and ventricular function in mice?
Cardiac-specific inhibition of Rho GTPases in mice causes progressive atrioventricular conduction defects without impairing basal ventricular contractile function.
Should not inform clinical practice; extends preclinical evidence linking Rho GTPases to AV conduction in mice.
Recent studies suggest that RhoA and Rac1 mediate hypertrophic signals in cardiac myocyte hypertrophy. However, effects on cardiac function caused by inhibition of their activity in the heart have yet to be evaluated. Cardiac-specific inhibition of Rho family protein activities was achieved by expressing Rho GDIalpha, an endogenous specific GDP dissociation inhibitor for Rho family proteins, using the alpha-myosin heavy-chain promoter. Increased expression of Rho GDIalpha led to atrial arrhythmias and mild ventricular hypertrophy in adult mice (4-7 months). However, left ventricular systolic and diastolic function was largely preserved before and after the development of cardiac hypertrophy, indicating that Rho GTPases are not required to maintain ventricular contractile function under basal physiological condition. Electrocardiography and intracardiac electrophysiological studies revealed first-degree atrioventricular (AV) block in the transgenic heart at 1 week of age, which further progressed into second-degree AV block at 4 weeks of age before the development of cardiac hypertrophy. Expression of connexin 40 dramatically decreased from 1 week to 4 weeks of age in the transgenic heart, which may contribute in part to the conduction defects in the transgenic mice. This study provides novel evidence for an important role of Rho GTPases in regulating AV conduction.
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Wei et al. (2004) studied Atrioventricular conduction defects and cardiac hypertrophy. Cardiac-specific expression of Rho GDIalpha was evaluated on Cardiac function and atrioventricular conduction. Cardiac-specific inhibition of Rho family proteins in mice led to progressive atrioventricular block and atrial arrhythmias, while preserving ventricular contractile function.
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