Cardiac remodeling and arrhythmogenesis are ameliorated by administration of Cx43 mimetic peptide Gap27 in heart failure rats
Lucero, Claudia M.
Pontificia Universidad Catolica de Chile
Andrade, David C.
Pontificia Universidad Catolica de Chile
Toledo, Camilo
Pontificia Universidad Catolica de Chile
Diaz, Hugo S.
Pontificia Universidad Catolica de Chile
Pereyra, Katherin V.
Pontificia Universidad Catolica de Chile
Diaz-Jara, Esteban
Pontificia Universidad Catolica de Chile
Schwarz, Karla G.
Pontificia Universidad Catolica de Chile
Marcus, Noah J.
Des Moines University
Retamal, Mauricio A.
Universidad del Desarrollo
Quintanilla, Rodrigo A.
Universidad Autonoma de Chile
Del Rio, Rodrigo
Journal
Scientific Reports
ISSN
2045-2322
Open Access
gold
Volume
10
Alterations in connexins and specifically in 43 isoform (Cx43) in the heart have been associated with a high incidence of arrhythmogenesis and sudden death in several cardiac diseases. We propose to determine salutary effect of Cx43 mimetic peptide Gap27 in the progression of heart failure. High-output heart failure was induced by volume overload using the arterio-venous fistula model (AV-Shunt) in adult male rats. Four weeks after AV-Shunt surgery, the Cx43 mimetic peptide Gap27 or scrambled peptide, were administered via osmotic minipumps (AV-Shunt(Gap27) or AV-Shunt(Scr)) for 4 weeks. Cardiac volumes, arrhythmias, function and remodeling were determined at 8 weeks after AV-Shunt surgeries. At 8(th) week, AV-Shunt(Gap27) showed a marked decrease in the progression of cardiac deterioration and showed a significant improvement in cardiac functions measured by intraventricular pressure-volume loops. Furthermore, AV-Shunt(Gap27) showed less cardiac arrhythmogenesis and cardiac hypertrophy index compared to AV-Shunt(Scr). Gap27 treatment results in no change Cx43 expression in the heart of AV-Shunt rats. Our results strongly suggest that Cx43 play a pivotal role in the progression of cardiac dysfunction and arrhythmogenesis in high-output heart failure; furthermore, support the use of Cx43 mimetic peptide Gap27 as an effective therapeutic tool to reduce the progression of cardiac dysfunction in high-output heart failure.
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