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.
authors.affiliation: Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, Ospedale S. Andrea, Rome 00189, Italy. rubattu.speranza@neuromed.it.
authors.forename: Speranza
authors.initials: S
authors.lastname: Rubattu
authors.forename: Silvia
authors.initials: S
authors.lastname: Mennuni
authors.forename: Marco
authors.initials: M
authors.lastname: Testa
authors.forename: Mara
authors.initials: M
authors.lastname: Mennuni
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pierelli
authors.forename: Beniamino
authors.initials: B
authors.lastname: Pagliaro
authors.forename: Erica
authors.initials: E
authors.lastname: Gabriele
authors.forename: Roberta
authors.initials: R
authors.lastname: Coluccia
authors.forename: Camillo
authors.initials: C
authors.lastname: Autore
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
mesh_terms: D059347:Cardio-Renal Syndrome / Q000209:etiology / Q000473:pathology*; D002908:Chronic Disease; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D012084:Renin-Angiotensin System; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000473:pathology