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

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
Artikelnummer103486
TidsskriftJournal of Proteomics
Vol/bind208
Antal sider11
ISSN1874-3919
DOI
StatusUdgivet - 30. sep. 2019

Fingeraftryk

CXC Chemokines
Chemokine Receptors
Angiotensins
Down-Regulation
angiotensin I (1-7)
Proteome
Renin-Angiotensin System
Cyclodextrins
Infarction
Renin
Wistar Rats
Rats
Animals
Repair
Anti-Inflammatory Agents
Chemical activation
Modulation

Citer dette

Gómez-Mendoza, Diana Paola ; Marques, Fúlvia Dias ; Melo-Braga, Marcella Nunes ; Sprenger, Richard R. ; Sinisterra, Rubén Dario ; Kjeldsen, Frank ; Santos, Robson Augusto ; Verano-Braga, Thiago. / Angiotensin-(1-7) oral treatment after experimental myocardial infarction leads to downregulation of CXCR4. I: Journal of Proteomics. 2019 ; Bind 208.
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title = "Angiotensin-(1-7) oral treatment after experimental myocardial infarction leads to downregulation of CXCR4",
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.",
keywords = "Angiotensin-(1–7), Anti-inflammatory, CXCR4, Myocardial infarction, Proteomics",
author = "G{\'o}mez-Mendoza, {Diana Paola} and Marques, {F{\'u}lvia Dias} and Melo-Braga, {Marcella Nunes} and Sprenger, {Richard R.} and Sinisterra, {Rub{\'e}n Dario} and Frank Kjeldsen and Santos, {Robson Augusto} and Thiago Verano-Braga",
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month = "9",
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Angiotensin-(1-7) oral treatment after experimental myocardial infarction leads to downregulation of CXCR4. / Gómez-Mendoza, Diana Paola; Marques, Fúlvia Dias; Melo-Braga, Marcella Nunes; Sprenger, Richard R.; Sinisterra, Rubén Dario; Kjeldsen, Frank; Santos, Robson Augusto; Verano-Braga, Thiago.

I: Journal of Proteomics, Bind 208, 103486, 30.09.2019.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Angiotensin-(1-7) oral treatment after experimental myocardial infarction leads to downregulation of CXCR4

AU - Gómez-Mendoza, Diana Paola

AU - Marques, Fúlvia Dias

AU - Melo-Braga, Marcella Nunes

AU - Sprenger, Richard R.

AU - Sinisterra, Rubén Dario

AU - Kjeldsen, Frank

AU - Santos, Robson Augusto

AU - Verano-Braga, Thiago

PY - 2019/9/30

Y1 - 2019/9/30

N2 - 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.

AB - 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.

KW - Angiotensin-(1–7)

KW - Anti-inflammatory

KW - CXCR4

KW - Myocardial infarction

KW - Proteomics

U2 - 10.1016/j.jprot.2019.103486

DO - 10.1016/j.jprot.2019.103486

M3 - Journal article

C2 - 31437601

AN - SCOPUS:85071026175

VL - 208

JO - Journal of Proteomics

JF - Journal of Proteomics

SN - 1874-3919

M1 - 103486

ER -