Cardiac remodeling and arrhythmogenesis are ameliorated by administration of Cx43 mimetic peptide Gap27 in heart failure rats
Journal
Scientific Reports
ISSN
2045-2322
Date Issued
2020
Author(s)
Claudia M. Lucero
David C. Andrade
Camilo Toledo
Hugo S. Díaz
Katherin V. Pereyra
Esteban Diaz-Jara
Karla G. Schwarz
Noah J. Marcus
Rodrigo A. Quintanilla
Rodrigo Del Rio
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:title>Abstract</jats:title><jats:p>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<jats:sub>Gap27</jats:sub> or AV-Shunt<jats:sub>Scr</jats:sub>) for 4 weeks. Cardiac volumes, arrhythmias, function and remodeling were determined at 8 weeks after AV-Shunt surgeries. At 8<jats:sup>th</jats:sup> week, AV-Shunt<jats:sub>Gap27</jats:sub> 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<jats:sub>Gap27</jats:sub> showed less cardiac arrhythmogenesis and cardiac hypertrophy index compared to AV-Shunt<jats:sub>Scr</jats:sub>. 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.</jats:p>
Cite this document
Lucero, C. M., Andrade, D. C., Toledo, C., Díaz, H. S., Pereyra, K. V., Diaz-Jara, E., Schwarz, K. G., Marcus, N. J., Retamal, M. A., Quintanilla, R. A., & Del Rio, R. (2020). Cardiac remodeling and arrhythmogenesis are ameliorated by administration of Cx43 mimetic peptide Gap27 in heart failure rats. Scientific Reports, 10(1), 6878. https://doi.org/10.1038/s41598-020-63336-6
Subjects
animals
;
arrhythmias, cardiac
;
arteriovenous shunt, surgical
;
cardiomegaly
;
connexin 43
;
fibrosis
;
heart failure
;
heart ventricles
;
hemodynamics
;
male
;
peptides
;
rats, sprague-dawley
;
vasodilation
;
ventricular remodeling
;
connexin 43
;
peptide
;
animal
;
arteriovenous shunt
;
cardiomegaly
;
chemistry
;
complication
;
diagnostic imaging
;
drug effect
;
fibrosis
;
heart arrhythmia
;
heart failure
;
heart ventricle
;
heart ventricle remodeling
;
hemodynamics
;
male
;
pathophysiology
;
sprague dawley rat
;
vasodilatation