Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure

Abstract

The kidney not only regulates fluid and electrolyte balance but also functions as an endocrine organ. For instance, it is the major source of circulating erythropoietin and renin. Despite currently available therapies, there is a marked increase in cardiovascular morbidity and mortality among patients suffering from end-stage renal disease. We hypothesized that the current understanding of the endocrine function of the kidney was incomplete and that the organ might secrete additional proteins with important biological roles. Here we report the identification of a novel flavin adenine dinucleotide-dependent amine oxidase (renalase) that is secreted into the blood by the kidney and metabolizes catecholamines in vitro (renalase metabolizes dopamine most efficiently, followed by epinephrine, and then norepinephrine). In humans, renalase gene expression is highest in the kidney but is also detectable in the heart, skeletal muscle, and the small intestine. The plasma concentration of renalase is markedly reduced in patients with end-stage renal disease, as compared with healthy subjects. Renalase infusion in rats caused a decrease in cardiac contractility, heart rate, and blood pressure and prevented a compensatory increase in peripheral vascular tone. These results identify renalase as what we believe to be a novel amine oxidase that is secreted by the kidney, circulates in blood, and modulates cardiac function and systemic blood pressure.

Renalase Gene Polymorphism in Patients with Hypertension and Concomitant Coronary Heart Disease

“…Renalase is involved in the regulation of blood pressure and cardiac function via degrading catecholamines in the blood circulation [3,4]. Human renalase gene is mapped to 10q23.33 [5] and highly expressed in the kidney and heart [6,7]. To date, available studies focus on the role of renalase gene polymorphism in the hypertension, and the single nucleotide polymorphisms (SNP) studied in previous studies is usually localized at the potential functional domains.…”

Lisinopril Protects Against the Adriamycin Nephropathy and Reverses the Renalase Reduction: Potential Role of Renalase in Adriamycin Nephropathy

“…Renalase is a novel flavin adenine dinucleotide-dependent amine oxidase, which was first discovered by Gary V. Desir in 2005 [1]. It has been shown that renalase can metabolize circulating catecholamines and regulate blood pressure.…”

“…It has been shown that renalase can metabolize circulating catecholamines and regulate blood pressure. Renalase consists of 342 amino acids, has a molecular weight of approximately 37.8 kDa, and is primarily distributed in the kidney, heart, skeletal muscle, and small intestine [1,2]. In renal tissue, renalase is primarily detected in renal tubular epithelial cells, mesangial cells and podocytes.…”

Quantification of Norepinephrine and Its Metabolites in the Plasma of Renal Failure Models

“…A new MAO enzyme named renalase, secreted mainly by kidney, was discovered to exist in the circulation [16]. The catalytic potency and gene expression of renalase are regulated by the concentration of circulating catecholamines [17,18].…”

“…It was shown that plasma renalase is markedly reduced in patients with chronic kidney disease and ESRD, and in animal models of chronic kidney disease and salt-dependent hypertension [17,18]. In rats, renalase infusion decreased cardiac contractility, heart rate, and blood pressure [16]. …”