Unilateral Acute Renal Ischemia-Reperfusion Injury Induces Cardiac Dysfunction through Intracellular Calcium Mishandling

Background: Acute renal failure (ARF) following renal ischemia-reperfusion (I/R) injury is considered a relevant risk factor for cardiac damage, but the underlying mechanisms, particularly those triggered at cardiomyocyte level, are unknown. Methods: We examined intracellular Ca<sup>2+</sup...

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Main Authors: Carolina Victoria Cruz Junho, Laura González-Lafuente, José Alberto Navarro-García, Elena Rodríguez-Sánchez, Marcela Sorelli Carneiro-Ramos, Gema Ruiz-Hurtado
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/4/2266
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author Carolina Victoria Cruz Junho
Laura González-Lafuente
José Alberto Navarro-García
Elena Rodríguez-Sánchez
Marcela Sorelli Carneiro-Ramos
Gema Ruiz-Hurtado
author_facet Carolina Victoria Cruz Junho
Laura González-Lafuente
José Alberto Navarro-García
Elena Rodríguez-Sánchez
Marcela Sorelli Carneiro-Ramos
Gema Ruiz-Hurtado
author_sort Carolina Victoria Cruz Junho
collection DOAJ
description Background: Acute renal failure (ARF) following renal ischemia-reperfusion (I/R) injury is considered a relevant risk factor for cardiac damage, but the underlying mechanisms, particularly those triggered at cardiomyocyte level, are unknown. Methods: We examined intracellular Ca<sup>2+</sup> dynamics in adult ventricular cardiomyocytes isolated from C57BL/6 mice 7 or 15 days following unilateral renal I/R. Results: After 7 days of I/R, the cell contraction was significantly lower in cardiomyocytes compared to sham-treated mice. It was accompanied by a significant decrease in both systolic Ca<sup>2+</sup> transients and sarco/endoplasmic reticulum Ca<sup>2+</sup>-ATPase (SERCA<sub>2a</sub>) activity measured as Ca<sup>2+</sup> transients decay. Moreover, the incidence of pro-arrhythmic events, measured as the number of Ca<sup>2+</sup> sparks, waves or automatic Ca<sup>2+</sup> transients, was greater in cardiomyocytes from mice 7 days after I/R than from sham-treated mice. Ca<sup>2+</sup> mishandling related to systolic Ca<sup>2+</sup> transients and contraction were recovered to sham values 15 days after I/R, but Ca<sup>2+</sup> sparks frequency and arrhythmic events remained elevated. Conclusions: Renal I/R injury causes a cardiomyocyte Ca<sup>2+</sup> cycle dysfunction at medium (contraction-relaxation dysfunction) and long term (Ca<sup>2+</sup> leak), after 7 and 15 days of renal reperfusion, respectively.
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spelling doaj.art-f95784e6626c452a9c36b5f249ec928d2023-11-23T20:22:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234226610.3390/ijms23042266Unilateral Acute Renal Ischemia-Reperfusion Injury Induces Cardiac Dysfunction through Intracellular Calcium MishandlingCarolina Victoria Cruz Junho0Laura González-Lafuente1José Alberto Navarro-García2Elena Rodríguez-Sánchez3Marcela Sorelli Carneiro-Ramos4Gema Ruiz-Hurtado5Center of Natural and Human Sciences (CCNH), Federal University of ABC, Santo André 09210-580, SP, BrazilCardiorenal Translational Laboratory, Institute of Research Imas12, Hospital Universitario 12 de Octubre, Community of Madrid, 28041 Madrid, SpainCardiorenal Translational Laboratory, Institute of Research Imas12, Hospital Universitario 12 de Octubre, Community of Madrid, 28041 Madrid, SpainCardiorenal Translational Laboratory, Institute of Research Imas12, Hospital Universitario 12 de Octubre, Community of Madrid, 28041 Madrid, SpainCenter of Natural and Human Sciences (CCNH), Federal University of ABC, Santo André 09210-580, SP, BrazilCardiorenal Translational Laboratory, Institute of Research Imas12, Hospital Universitario 12 de Octubre, Community of Madrid, 28041 Madrid, SpainBackground: Acute renal failure (ARF) following renal ischemia-reperfusion (I/R) injury is considered a relevant risk factor for cardiac damage, but the underlying mechanisms, particularly those triggered at cardiomyocyte level, are unknown. Methods: We examined intracellular Ca<sup>2+</sup> dynamics in adult ventricular cardiomyocytes isolated from C57BL/6 mice 7 or 15 days following unilateral renal I/R. Results: After 7 days of I/R, the cell contraction was significantly lower in cardiomyocytes compared to sham-treated mice. It was accompanied by a significant decrease in both systolic Ca<sup>2+</sup> transients and sarco/endoplasmic reticulum Ca<sup>2+</sup>-ATPase (SERCA<sub>2a</sub>) activity measured as Ca<sup>2+</sup> transients decay. Moreover, the incidence of pro-arrhythmic events, measured as the number of Ca<sup>2+</sup> sparks, waves or automatic Ca<sup>2+</sup> transients, was greater in cardiomyocytes from mice 7 days after I/R than from sham-treated mice. Ca<sup>2+</sup> mishandling related to systolic Ca<sup>2+</sup> transients and contraction were recovered to sham values 15 days after I/R, but Ca<sup>2+</sup> sparks frequency and arrhythmic events remained elevated. Conclusions: Renal I/R injury causes a cardiomyocyte Ca<sup>2+</sup> cycle dysfunction at medium (contraction-relaxation dysfunction) and long term (Ca<sup>2+</sup> leak), after 7 and 15 days of renal reperfusion, respectively.https://www.mdpi.com/1422-0067/23/4/2266renal ischemia and reperfusionintracellular calcium handlingadult cardiomyocytecardiorenal syndromeacute renal failure
spellingShingle Carolina Victoria Cruz Junho
Laura González-Lafuente
José Alberto Navarro-García
Elena Rodríguez-Sánchez
Marcela Sorelli Carneiro-Ramos
Gema Ruiz-Hurtado
Unilateral Acute Renal Ischemia-Reperfusion Injury Induces Cardiac Dysfunction through Intracellular Calcium Mishandling
International Journal of Molecular Sciences
renal ischemia and reperfusion
intracellular calcium handling
adult cardiomyocyte
cardiorenal syndrome
acute renal failure
title Unilateral Acute Renal Ischemia-Reperfusion Injury Induces Cardiac Dysfunction through Intracellular Calcium Mishandling
title_full Unilateral Acute Renal Ischemia-Reperfusion Injury Induces Cardiac Dysfunction through Intracellular Calcium Mishandling
title_fullStr Unilateral Acute Renal Ischemia-Reperfusion Injury Induces Cardiac Dysfunction through Intracellular Calcium Mishandling
title_full_unstemmed Unilateral Acute Renal Ischemia-Reperfusion Injury Induces Cardiac Dysfunction through Intracellular Calcium Mishandling
title_short Unilateral Acute Renal Ischemia-Reperfusion Injury Induces Cardiac Dysfunction through Intracellular Calcium Mishandling
title_sort unilateral acute renal ischemia reperfusion injury induces cardiac dysfunction through intracellular calcium mishandling
topic renal ischemia and reperfusion
intracellular calcium handling
adult cardiomyocyte
cardiorenal syndrome
acute renal failure
url https://www.mdpi.com/1422-0067/23/4/2266
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