Angiotensin-(1-7) oral treatment after experimental myocardial infarction leads to downregulation of CXCR4

Diana Paola Gómez-Mendoza, Fúlvia Dias Marques, Marcella Nunes Melo-Braga, Richard R. Sprenger, Rubén Dario Sinisterra, Frank Kjeldsen, Robson Augusto Santos*, Thiago Verano-Braga

*Corresponding author for this work

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Abstract

Myocardial infarction triggers cellular events that starts with the activation of inflammatory response and fibrogenic pathways involved in cardiac tissue remodeling. Angiotensin-(1–7) (Ang-(1–7)) is an endogenous heptapeptide from the renin-angiotensin system with a cardioprotective role due to its anti-inflammatory and anti-fibrotic activities in cardiac cells. Although the beneficial aspects of Ang-(1–7) in animal models of cardiac ischemia have been reported, the molecular events underlying Ang-(1–7) cardioprotective effect remains elusive. This study investigated the impact of oral treatment with Ang-(1–7) included in hydroxypropyl β-cyclodextrin (HPβCD/Ang-(1–7)) on the cardiac proteome dysregulation due to experimental myocardial infarction. Wistar male rats were submitted to experimental myocardial infarction and treated daily with HPβCD/Ang-(1–7) during 7 days or 60 days by gavage. Our results showed that HPβCD/Ang-(1–7) treatment ameliorates the post-infarction condition due to the modulation of proteins that initially favor the resolution of inflammation and mitochondrial dysfunction. Moreover, this study reported for the first time that Ang-(1–7) treatment after experimental myocardial infarction leads to the downregulation of the C-X-C chemokine receptor type 4 (CXCR4). Significance: Myocardial infarction triggers a sequence of cellular and molecular events that starts with an intense inflammatory response that is resolved in the proliferative phase. Prolonged inflammatory phase can lead to adverse cardiac repair and heart failure. In this context, we proposed a post-MI treatment using Ang-(1–7) included in HPβCD and administrated orally. We observed that HPβCD/Ang-(1–7) treatment led to CXCR4 downregulation, highlighting this C-X-C chemokine receptor as a potential therapeutic target for ischemic heart diseases.

Original languageEnglish
Article number103486
JournalJournal of Proteomics
Volume208
Number of pages11
ISSN1874-3919
DOIs
Publication statusPublished - 30. Sep 2019

Keywords

  • Angiotensin-(1–7)
  • Anti-inflammatory
  • CXCR4
  • Myocardial infarction
  • Proteomics

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