title: Human renalase: a review of its biology, function, and implications for hypertension.
abstract: Renalase is a novel flavoprotein, highly expressed in kidney and heart, which metabolizes catecholamines and catecholamine-like substances via a superoxide (O2(-))-dependent mechanism using nicotinamide adenine dinucleotide (NADH) as a cofactor. Its mechanism of action is distinct from that of monoaminooxidases A and B, because it oxidizes catecholamines (epinephrine>>L-DOPA>dopamine = norepinephrine) to aminochrome, and the reaction rate increases ∼4- to 6-fold in presence of NADH. Tissue and plasma renalase levels are decreased in animal models of chronic kidney disease, and renalase deficiency is associated with increased blood pressure and elevated circulating catecholamines. Renalase plasma levels, measured by enzyme-linked immunosorbent assay, are reported to be ∼ 5-fold higher in patients with end-stage renal disease than in normal control subjects. They were also increased in kidney and heart transplant recipients, and inversely correlated with estimated glomerular filtration rate. Renalase has potential therapeutic applications. Experimental models demonstrate that the chronic administration of renalase decreases ambulatory blood pressure and prevents the development of cardiac hypertrophy in rats, and that its acute administration decreases ischemic acute kidney injury in mice. Here we provide a detailed review of renalase biology including its mechanism of action, secretion into blood, interaction with the renal dopamine and epinephrine system, and early studies evaluating its association with outcomes related to hypertension and target-organ injury.
authors.affiliation: Medical Service, VA Connecticut Healthcare System, West Haven, CT, USA. gary.desir@yale.edu
authors.forename: Gary V
authors.initials: GV
authors.lastname: Desir
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Aldo J
authors.initials: AJ
authors.lastname: Peixoto
mesh_terms: D000818:Animals; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000209:etiology* / Q000628:therapy*; D007674:Kidney Diseases / Q000150:complications / Q000201:enzymology / Q000628:therapy; D051379:Mice; D008995:Monoamine Oxidase / Q000502:physiology* / Q000627:therapeutic use; D051381:Rats
chemical_list: D008995:Monoamine Oxidase; C521557:renalase