Pathogenesis of chronic cardiorenal syndrome: Is there a role for oxidative stress?

Speranza Rubattu, Silvia Mennuni, Marco Testa, Mara Mennuni, Giorgia Pierelli, Beniamino Pagliaro, Erica Gabriele, Roberta Coluccia, Camillo Autore, Massimo Volpe

Research output: Contribution to journalArticle

Abstract

Cardiorenal syndrome is a frequently encountered clinical condition when the dysfunction of either the heart or kidneys amplifies the failure progression of the other organ. Complex biochemical, hormonal and hemodynamic mechanisms underlie the development of cardiorenal syndrome. Both in vitro and experimental studies have identified several dysregulated pathways in heart failure and in chronic kidney disease that lead to increased oxidative stress. A decrease in mitochondrial oxidative metabolism has been reported in cardiomyocytes during heart failure. This is balanced by a compensatory increase in glucose uptake and glycolysis with consequent decrease in myocardial ATP content. In the kidneys, both NADPH oxidase and mitochondrial metabolism are important sources of TGF-β1-induced cellular ROS. NOX-dependent oxidative activation of transcription factors such as NF-kB and c-jun leads to increased expression of renal target genes (phospholipaseA2, MCP-1 and CSF-1, COX-2), thus contributing to renal interstitial fibrosis and inflammation. In the present article, we postulate that, besides contributing to both cardiac and renal dysfunction, increased oxidative stress may also play a crucial role in cardiorenal syndrome development and progression. In particular, an imbalance between the renin-angiotensin-aldosterone system, the sympathetic nervous system, and inflammation may favour cardiorenal syndrome through an excessive oxidative stress production. This article also discusses novel therapeutic strategies for their potential use in the treatment of patients affected by cardiorenal syndrome.

Original languageEnglish
Pages (from-to)23011-23032
Number of pages22
JournalInternational Journal of Molecular Sciences
Volume14
Issue number11
DOIs
Publication statusPublished - Nov 20 2013

Fingerprint

Cardio-Renal Syndrome
pathogenesis
Oxidative stress
Oxidative Stress
Metabolism
Kidney
kidneys
metabolism
Macrophage Colony-Stimulating Factor
Transcription factors
progressions
NF-kappa B
NADPH Oxidase
Adenosinetriphosphate
Angiotensins
Hemodynamics
Neurology
sympathetic nervous system
aldosterone
Aldosterone

Keywords

  • Heart failure
  • Inflammation
  • Mitochondrial dysfunction
  • Oxidative stress
  • Renal failure
  • Renin-angiotensin-aldosterone system
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Computer Science Applications
  • Molecular Biology
  • Catalysis
  • Inorganic Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Physical and Theoretical Chemistry

Cite this

Pathogenesis of chronic cardiorenal syndrome : Is there a role for oxidative stress? / Rubattu, Speranza; Mennuni, Silvia; Testa, Marco; Mennuni, Mara; Pierelli, Giorgia; Pagliaro, Beniamino; Gabriele, Erica; Coluccia, Roberta; Autore, Camillo; Volpe, Massimo.

In: International Journal of Molecular Sciences, Vol. 14, No. 11, 20.11.2013, p. 23011-23032.

Research output: Contribution to journalArticle

Rubattu, S, Mennuni, S, Testa, M, Mennuni, M, Pierelli, G, Pagliaro, B, Gabriele, E, Coluccia, R, Autore, C & Volpe, M 2013, 'Pathogenesis of chronic cardiorenal syndrome: Is there a role for oxidative stress?', International Journal of Molecular Sciences, vol. 14, no. 11, pp. 23011-23032. https://doi.org/10.3390/ijms141123011
Rubattu, Speranza ; Mennuni, Silvia ; Testa, Marco ; Mennuni, Mara ; Pierelli, Giorgia ; Pagliaro, Beniamino ; Gabriele, Erica ; Coluccia, Roberta ; Autore, Camillo ; Volpe, Massimo. / Pathogenesis of chronic cardiorenal syndrome : Is there a role for oxidative stress?. In: International Journal of Molecular Sciences. 2013 ; Vol. 14, No. 11. pp. 23011-23032.
@article{f0d040739f0344e2831021feaf4e094a,
title = "Pathogenesis of chronic cardiorenal syndrome: Is there a role for oxidative stress?",
abstract = "Cardiorenal syndrome is a frequently encountered clinical condition when the dysfunction of either the heart or kidneys amplifies the failure progression of the other organ. Complex biochemical, hormonal and hemodynamic mechanisms underlie the development of cardiorenal syndrome. Both in vitro and experimental studies have identified several dysregulated pathways in heart failure and in chronic kidney disease that lead to increased oxidative stress. A decrease in mitochondrial oxidative metabolism has been reported in cardiomyocytes during heart failure. This is balanced by a compensatory increase in glucose uptake and glycolysis with consequent decrease in myocardial ATP content. In the kidneys, both NADPH oxidase and mitochondrial metabolism are important sources of TGF-β1-induced cellular ROS. NOX-dependent oxidative activation of transcription factors such as NF-kB and c-jun leads to increased expression of renal target genes (phospholipaseA2, MCP-1 and CSF-1, COX-2), thus contributing to renal interstitial fibrosis and inflammation. In the present article, we postulate that, besides contributing to both cardiac and renal dysfunction, increased oxidative stress may also play a crucial role in cardiorenal syndrome development and progression. In particular, an imbalance between the renin-angiotensin-aldosterone system, the sympathetic nervous system, and inflammation may favour cardiorenal syndrome through an excessive oxidative stress production. This article also discusses novel therapeutic strategies for their potential use in the treatment of patients affected by cardiorenal syndrome.",
keywords = "Heart failure, Inflammation, Mitochondrial dysfunction, Oxidative stress, Renal failure, Renin-angiotensin-aldosterone system, Sympathetic nervous system",
author = "Speranza Rubattu and Silvia Mennuni and Marco Testa and Mara Mennuni and Giorgia Pierelli and Beniamino Pagliaro and Erica Gabriele and Roberta Coluccia and Camillo Autore and Massimo Volpe",
year = "2013",
month = "11",
day = "20",
doi = "10.3390/ijms141123011",
language = "English",
volume = "14",
pages = "23011--23032",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "11",

}

TY - JOUR

T1 - Pathogenesis of chronic cardiorenal syndrome

T2 - Is there a role for oxidative stress?

AU - Rubattu, Speranza

AU - Mennuni, Silvia

AU - Testa, Marco

AU - Mennuni, Mara

AU - Pierelli, Giorgia

AU - Pagliaro, Beniamino

AU - Gabriele, Erica

AU - Coluccia, Roberta

AU - Autore, Camillo

AU - Volpe, Massimo

PY - 2013/11/20

Y1 - 2013/11/20

N2 - Cardiorenal syndrome is a frequently encountered clinical condition when the dysfunction of either the heart or kidneys amplifies the failure progression of the other organ. Complex biochemical, hormonal and hemodynamic mechanisms underlie the development of cardiorenal syndrome. Both in vitro and experimental studies have identified several dysregulated pathways in heart failure and in chronic kidney disease that lead to increased oxidative stress. A decrease in mitochondrial oxidative metabolism has been reported in cardiomyocytes during heart failure. This is balanced by a compensatory increase in glucose uptake and glycolysis with consequent decrease in myocardial ATP content. In the kidneys, both NADPH oxidase and mitochondrial metabolism are important sources of TGF-β1-induced cellular ROS. NOX-dependent oxidative activation of transcription factors such as NF-kB and c-jun leads to increased expression of renal target genes (phospholipaseA2, MCP-1 and CSF-1, COX-2), thus contributing to renal interstitial fibrosis and inflammation. In the present article, we postulate that, besides contributing to both cardiac and renal dysfunction, increased oxidative stress may also play a crucial role in cardiorenal syndrome development and progression. In particular, an imbalance between the renin-angiotensin-aldosterone system, the sympathetic nervous system, and inflammation may favour cardiorenal syndrome through an excessive oxidative stress production. This article also discusses novel therapeutic strategies for their potential use in the treatment of patients affected by cardiorenal syndrome.

AB - Cardiorenal syndrome is a frequently encountered clinical condition when the dysfunction of either the heart or kidneys amplifies the failure progression of the other organ. Complex biochemical, hormonal and hemodynamic mechanisms underlie the development of cardiorenal syndrome. Both in vitro and experimental studies have identified several dysregulated pathways in heart failure and in chronic kidney disease that lead to increased oxidative stress. A decrease in mitochondrial oxidative metabolism has been reported in cardiomyocytes during heart failure. This is balanced by a compensatory increase in glucose uptake and glycolysis with consequent decrease in myocardial ATP content. In the kidneys, both NADPH oxidase and mitochondrial metabolism are important sources of TGF-β1-induced cellular ROS. NOX-dependent oxidative activation of transcription factors such as NF-kB and c-jun leads to increased expression of renal target genes (phospholipaseA2, MCP-1 and CSF-1, COX-2), thus contributing to renal interstitial fibrosis and inflammation. In the present article, we postulate that, besides contributing to both cardiac and renal dysfunction, increased oxidative stress may also play a crucial role in cardiorenal syndrome development and progression. In particular, an imbalance between the renin-angiotensin-aldosterone system, the sympathetic nervous system, and inflammation may favour cardiorenal syndrome through an excessive oxidative stress production. This article also discusses novel therapeutic strategies for their potential use in the treatment of patients affected by cardiorenal syndrome.

KW - Heart failure

KW - Inflammation

KW - Mitochondrial dysfunction

KW - Oxidative stress

KW - Renal failure

KW - Renin-angiotensin-aldosterone system

KW - Sympathetic nervous system

UR - http://www.scopus.com/inward/record.url?scp=84888117591&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888117591&partnerID=8YFLogxK

U2 - 10.3390/ijms141123011

DO - 10.3390/ijms141123011

M3 - Article

C2 - 24264044

AN - SCOPUS:84888117591

VL - 14

SP - 23011

EP - 23032

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 11

ER -