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...
Main Authors: | , , , , , |
---|---|
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 |
_version_ | 1797479351633051648 |
---|---|
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. |
first_indexed | 2024-03-09T21:44:37Z |
format | Article |
id | doaj.art-f95784e6626c452a9c36b5f249ec928d |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-09T21:44:37Z |
publishDate | 2022-02-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
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 |
work_keys_str_mv | AT carolinavictoriacruzjunho unilateralacuterenalischemiareperfusioninjuryinducescardiacdysfunctionthroughintracellularcalciummishandling AT lauragonzalezlafuente unilateralacuterenalischemiareperfusioninjuryinducescardiacdysfunctionthroughintracellularcalciummishandling AT josealbertonavarrogarcia unilateralacuterenalischemiareperfusioninjuryinducescardiacdysfunctionthroughintracellularcalciummishandling AT elenarodriguezsanchez unilateralacuterenalischemiareperfusioninjuryinducescardiacdysfunctionthroughintracellularcalciummishandling AT marcelasorellicarneiroramos unilateralacuterenalischemiareperfusioninjuryinducescardiacdysfunctionthroughintracellularcalciummishandling AT gemaruizhurtado unilateralacuterenalischemiareperfusioninjuryinducescardiacdysfunctionthroughintracellularcalciummishandling |