Protection of the myocardium against ischemia/reperfusion injury by angiotensin-(1–9) through an AT2R and Akt-dependent mechanism

Evelyn Mendoza-Torres, Jaime A. Riquelme, Alejandra Vielma, Andrea Ramirez Sagredo, Luigi Gabrielli, Roberto Bravo-Sagua, Jorge E. Jalil, Beverly A. Rothermel, Gina Sanchez, Maria Paz Ocaranza, Sergio Lavandero

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Angiotensin-(19), a peptide of the non-classical renin angiotensin system, has been shown to prevent and revert hypertension and cardiac hypertrophy. We hypothetized that systemic delivery of angiotensin-(1–9) following myocardial infarction will also be protective and extend to provide protection during reperfusion of the ischemic heart. Adult Sprague Dawley rats were subjected to left anterior descending artery ligation and treated with angiotensin-(1–9) via osmotic mini-pump for 2 weeks in the presence or absence of Mas receptor or AT2R antagonists (A779 and PD123319, respectively). Myocardial death and left ventricular function were evaluated after infarction. Infarct size and functional parameters were determined in isolated rat hearts after global ischemia/reperfusion in the presence of angiotensin-(1–9) plus receptor antagonists or Akt inhibitor at reperfusion. in vitro, neonatal rat ventricular cardiomyocytes underwent simulated ischemia/reperfusion and angiotensin-(1–9) was co-incubated with A779, PD123319 or Akt inhibitor. Systemic delivery of angiotensin-(1–9) significantly decreased cell death and improved left ventricular recovery after in vivo myocardial infarction. Perfusion with the peptide reduced the infarct size and improved functional recovery after ex vivo ischemia/reperfusion. In vitro, angiotensin-(1–9) decreased cell death in isolated neonatal rat ventricular cardiomyocytes subjected to simulated ischemia/reperfusion. The cardioprotective effects of angiotensin-(1–9) were blocked by PD123319 and Akti VIII but not by A779. Angiotensin-(1–9) limits reperfusion-induced cell death by an AT2R- and Aktdependent mechanism. Angiotensin-(1–9) is a novel strategy to protect against cardiac ischemia/reperfusion injury.

Original languageEnglish (US)
Pages (from-to)112-121
Number of pages10
JournalPharmacological Research
Volume135
DOIs
StatePublished - Sep 1 2018

Fingerprint

Angiotensins
Reperfusion Injury
Myocardium
Reperfusion
7-Ala-angiotensin (1-7)
Ischemia
Cell Death
Cardiac Myocytes
Myocardial Infarction
Peptides
Cardiomegaly
Renin-Angiotensin System
Left Ventricular Function
Infarction
Ligation
Sprague Dawley Rats
Arteries
Perfusion
Hypertension

Keywords

  • 2,3,5-Triphenyltetrazolium chloride (CID: 9283)
  • 2-deoxy-D-glucose (CID: 108223)
  • A779 (CID: 10169886)
  • Akt inhibitor VIII (CID: 10196499)
  • Angiotensin type 2 receptor
  • Angiotensin-(1–9)
  • Angiotensin-(1–9) (CID: 71745056)
  • Cardioprotection
  • Heparin (CID: 772)
  • ischemia/reperfusion
  • Lactic acid (CID: 329761959)
  • PD123319 (CID: 5311345)
  • Pentobarbital (CID: 4737)
  • Propidium iodide (CID: 104981)
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Pharmacology

Cite this

Mendoza-Torres, E., Riquelme, J. A., Vielma, A., Sagredo, A. R., Gabrielli, L., Bravo-Sagua, R., ... Lavandero, S. (2018). Protection of the myocardium against ischemia/reperfusion injury by angiotensin-(1–9) through an AT2R and Akt-dependent mechanism. Pharmacological Research, 135, 112-121. https://doi.org/10.1016/j.phrs.2018.07.022

Protection of the myocardium against ischemia/reperfusion injury by angiotensin-(1–9) through an AT2R and Akt-dependent mechanism. / Mendoza-Torres, Evelyn; Riquelme, Jaime A.; Vielma, Alejandra; Sagredo, Andrea Ramirez; Gabrielli, Luigi; Bravo-Sagua, Roberto; Jalil, Jorge E.; Rothermel, Beverly A.; Sanchez, Gina; Ocaranza, Maria Paz; Lavandero, Sergio.

In: Pharmacological Research, Vol. 135, 01.09.2018, p. 112-121.

Research output: Contribution to journalArticle

Mendoza-Torres, E, Riquelme, JA, Vielma, A, Sagredo, AR, Gabrielli, L, Bravo-Sagua, R, Jalil, JE, Rothermel, BA, Sanchez, G, Ocaranza, MP & Lavandero, S 2018, 'Protection of the myocardium against ischemia/reperfusion injury by angiotensin-(1–9) through an AT2R and Akt-dependent mechanism', Pharmacological Research, vol. 135, pp. 112-121. https://doi.org/10.1016/j.phrs.2018.07.022
Mendoza-Torres, Evelyn ; Riquelme, Jaime A. ; Vielma, Alejandra ; Sagredo, Andrea Ramirez ; Gabrielli, Luigi ; Bravo-Sagua, Roberto ; Jalil, Jorge E. ; Rothermel, Beverly A. ; Sanchez, Gina ; Ocaranza, Maria Paz ; Lavandero, Sergio. / Protection of the myocardium against ischemia/reperfusion injury by angiotensin-(1–9) through an AT2R and Akt-dependent mechanism. In: Pharmacological Research. 2018 ; Vol. 135. pp. 112-121.
@article{fd1e935cda904b709ad053531c13278c,
title = "Protection of the myocardium against ischemia/reperfusion injury by angiotensin-(1–9) through an AT2R and Akt-dependent mechanism",
abstract = "Angiotensin-(19), a peptide of the non-classical renin angiotensin system, has been shown to prevent and revert hypertension and cardiac hypertrophy. We hypothetized that systemic delivery of angiotensin-(1–9) following myocardial infarction will also be protective and extend to provide protection during reperfusion of the ischemic heart. Adult Sprague Dawley rats were subjected to left anterior descending artery ligation and treated with angiotensin-(1–9) via osmotic mini-pump for 2 weeks in the presence or absence of Mas receptor or AT2R antagonists (A779 and PD123319, respectively). Myocardial death and left ventricular function were evaluated after infarction. Infarct size and functional parameters were determined in isolated rat hearts after global ischemia/reperfusion in the presence of angiotensin-(1–9) plus receptor antagonists or Akt inhibitor at reperfusion. in vitro, neonatal rat ventricular cardiomyocytes underwent simulated ischemia/reperfusion and angiotensin-(1–9) was co-incubated with A779, PD123319 or Akt inhibitor. Systemic delivery of angiotensin-(1–9) significantly decreased cell death and improved left ventricular recovery after in vivo myocardial infarction. Perfusion with the peptide reduced the infarct size and improved functional recovery after ex vivo ischemia/reperfusion. In vitro, angiotensin-(1–9) decreased cell death in isolated neonatal rat ventricular cardiomyocytes subjected to simulated ischemia/reperfusion. The cardioprotective effects of angiotensin-(1–9) were blocked by PD123319 and Akti VIII but not by A779. Angiotensin-(1–9) limits reperfusion-induced cell death by an AT2R- and Aktdependent mechanism. Angiotensin-(1–9) is a novel strategy to protect against cardiac ischemia/reperfusion injury.",
keywords = "2,3,5-Triphenyltetrazolium chloride (CID: 9283), 2-deoxy-D-glucose (CID: 108223), A779 (CID: 10169886), Akt inhibitor VIII (CID: 10196499), Angiotensin type 2 receptor, Angiotensin-(1–9), Angiotensin-(1–9) (CID: 71745056), Cardioprotection, Heparin (CID: 772), ischemia/reperfusion, Lactic acid (CID: 329761959), PD123319 (CID: 5311345), Pentobarbital (CID: 4737), Propidium iodide (CID: 104981), Renin-angiotensin system",
author = "Evelyn Mendoza-Torres and Riquelme, {Jaime A.} and Alejandra Vielma and Sagredo, {Andrea Ramirez} and Luigi Gabrielli and Roberto Bravo-Sagua and Jalil, {Jorge E.} and Rothermel, {Beverly A.} and Gina Sanchez and Ocaranza, {Maria Paz} and Sergio Lavandero",
year = "2018",
month = "9",
day = "1",
doi = "10.1016/j.phrs.2018.07.022",
language = "English (US)",
volume = "135",
pages = "112--121",
journal = "Pharmacological Research",
issn = "1043-6618",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Protection of the myocardium against ischemia/reperfusion injury by angiotensin-(1–9) through an AT2R and Akt-dependent mechanism

AU - Mendoza-Torres, Evelyn

AU - Riquelme, Jaime A.

AU - Vielma, Alejandra

AU - Sagredo, Andrea Ramirez

AU - Gabrielli, Luigi

AU - Bravo-Sagua, Roberto

AU - Jalil, Jorge E.

AU - Rothermel, Beverly A.

AU - Sanchez, Gina

AU - Ocaranza, Maria Paz

AU - Lavandero, Sergio

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Angiotensin-(19), a peptide of the non-classical renin angiotensin system, has been shown to prevent and revert hypertension and cardiac hypertrophy. We hypothetized that systemic delivery of angiotensin-(1–9) following myocardial infarction will also be protective and extend to provide protection during reperfusion of the ischemic heart. Adult Sprague Dawley rats were subjected to left anterior descending artery ligation and treated with angiotensin-(1–9) via osmotic mini-pump for 2 weeks in the presence or absence of Mas receptor or AT2R antagonists (A779 and PD123319, respectively). Myocardial death and left ventricular function were evaluated after infarction. Infarct size and functional parameters were determined in isolated rat hearts after global ischemia/reperfusion in the presence of angiotensin-(1–9) plus receptor antagonists or Akt inhibitor at reperfusion. in vitro, neonatal rat ventricular cardiomyocytes underwent simulated ischemia/reperfusion and angiotensin-(1–9) was co-incubated with A779, PD123319 or Akt inhibitor. Systemic delivery of angiotensin-(1–9) significantly decreased cell death and improved left ventricular recovery after in vivo myocardial infarction. Perfusion with the peptide reduced the infarct size and improved functional recovery after ex vivo ischemia/reperfusion. In vitro, angiotensin-(1–9) decreased cell death in isolated neonatal rat ventricular cardiomyocytes subjected to simulated ischemia/reperfusion. The cardioprotective effects of angiotensin-(1–9) were blocked by PD123319 and Akti VIII but not by A779. Angiotensin-(1–9) limits reperfusion-induced cell death by an AT2R- and Aktdependent mechanism. Angiotensin-(1–9) is a novel strategy to protect against cardiac ischemia/reperfusion injury.

AB - Angiotensin-(19), a peptide of the non-classical renin angiotensin system, has been shown to prevent and revert hypertension and cardiac hypertrophy. We hypothetized that systemic delivery of angiotensin-(1–9) following myocardial infarction will also be protective and extend to provide protection during reperfusion of the ischemic heart. Adult Sprague Dawley rats were subjected to left anterior descending artery ligation and treated with angiotensin-(1–9) via osmotic mini-pump for 2 weeks in the presence or absence of Mas receptor or AT2R antagonists (A779 and PD123319, respectively). Myocardial death and left ventricular function were evaluated after infarction. Infarct size and functional parameters were determined in isolated rat hearts after global ischemia/reperfusion in the presence of angiotensin-(1–9) plus receptor antagonists or Akt inhibitor at reperfusion. in vitro, neonatal rat ventricular cardiomyocytes underwent simulated ischemia/reperfusion and angiotensin-(1–9) was co-incubated with A779, PD123319 or Akt inhibitor. Systemic delivery of angiotensin-(1–9) significantly decreased cell death and improved left ventricular recovery after in vivo myocardial infarction. Perfusion with the peptide reduced the infarct size and improved functional recovery after ex vivo ischemia/reperfusion. In vitro, angiotensin-(1–9) decreased cell death in isolated neonatal rat ventricular cardiomyocytes subjected to simulated ischemia/reperfusion. The cardioprotective effects of angiotensin-(1–9) were blocked by PD123319 and Akti VIII but not by A779. Angiotensin-(1–9) limits reperfusion-induced cell death by an AT2R- and Aktdependent mechanism. Angiotensin-(1–9) is a novel strategy to protect against cardiac ischemia/reperfusion injury.

KW - 2,3,5-Triphenyltetrazolium chloride (CID: 9283)

KW - 2-deoxy-D-glucose (CID: 108223)

KW - A779 (CID: 10169886)

KW - Akt inhibitor VIII (CID: 10196499)

KW - Angiotensin type 2 receptor

KW - Angiotensin-(1–9)

KW - Angiotensin-(1–9) (CID: 71745056)

KW - Cardioprotection

KW - Heparin (CID: 772)

KW - ischemia/reperfusion

KW - Lactic acid (CID: 329761959)

KW - PD123319 (CID: 5311345)

KW - Pentobarbital (CID: 4737)

KW - Propidium iodide (CID: 104981)

KW - Renin-angiotensin system

UR - http://www.scopus.com/inward/record.url?scp=85050997614&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050997614&partnerID=8YFLogxK

U2 - 10.1016/j.phrs.2018.07.022

DO - 10.1016/j.phrs.2018.07.022

M3 - Article

C2 - 30048754

AN - SCOPUS:85050997614

VL - 135

SP - 112

EP - 121

JO - Pharmacological Research

JF - Pharmacological Research

SN - 1043-6618

ER -