Disruption of Rho signaling results in progressive atrioventricular conduction defects while ventricular function remains preserved.

Lei Wei, George E. Taffet, Dirar S. Khoury, Jacqueline Bo, Y. Li, Atsuko Yatani, M. Craig Delaughter, Raisa Klevitsky, Timothy E. Hewett, Jeffrey Robbins, Lloyd H. Michael, Michael D. Schneider, Mark L. Entman, Robert J. Schwartz

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34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)857-859
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume18
Issue number7
StatePublished - May 2004

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Wei, L., Taffet, G. E., Khoury, D. S., Bo, J., Li, Y., Yatani, A., Delaughter, M. C., Klevitsky, R., Hewett, T. E., Robbins, J., Michael, L. H., Schneider, M. D., Entman, M. L., & Schwartz, R. J. (2004). Disruption of Rho signaling results in progressive atrioventricular conduction defects while ventricular function remains preserved. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 18(7), 857-859.