Saturday, April 23, 2005


From U.S. News & World Report:

Patients with end-stage kidney disease also face a much higher risk of heart disease. Scientists say they've uncovered a pathway that could explain this: a previously unknown protein that may act as a powerful modulator of cardiovascular function. They combed through 114 genes, looking for ones that would be particularly active in the kidneys. A deficiency of one (now dubbed renalase) looks like the culprit.

Renalase appears to help metabolize excess adrenaline, a hormone that jump-starts heart rate and blood pressure and can prompt heart attacks. Yale University's Jianchao Xu, lead author of the paper in the Journal of Clinical Investigation, speculates that renalase may someday offer a treatment for the country's No. 1 killer, heart disease.

From JCI:

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

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.

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