Inhibition of c-Src tyrosine kinase prevents angiotensin II-mediated connexin-43 remodeling and sudden cardiac death.

ABSTRACT:

Objectives

The aim of this study was to test whether c-Src tyrosine kinase mediates connexin-43 (Cx43) reduction and sudden cardiac death in a transgenic mouse model of cardiac-restricted overexpression of angiotensin-converting enzyme (ACE8/8 mice).

Background

Renin-angiotensin system activation is associated with an increased risk for arrhythmia and sudden cardiac death, but the mechanism is not well understood. The up-regulation of c-Src by angiotensin II may result in the reduction of Cx43, which impairs gap junction function and provides a substrate for arrhythmia.

Methods

Wild-type and ACE8/8 mice with and without treatment with the c-Src inhibitor 1-(1,1-dimethylethyl)-1-(4-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (PP1) were studied. Telemetry monitori

SUBMITTER: Sovari AA 

PROVIDER: S-EPMC3226807 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature