Uric acid-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP concentrations.

Abstract

BACKGROUND/AIMS:

Endothelial dysfunction is associated with mitochondrial alterations. We hypothesized that uric acid (UA), which can induce endothelial dysfunction in vitro and in vivo, might also alter mitochondrial function.

METHODS:

Human aortic endothelial cells were exposed to soluble UA and measurements of oxidative stress, nitric oxide, mitochondrial density, ATP production, aconitase-2 and enoyl Co-A hydratase-1 expressions, and aconitase-2 activity in isolated mitochondria were determined. The effect of hyperuricemia induced by uricase inhibition in rats on renal mitochondrial integrity was also assessed.

RESULTS:

UA-induced endothelial dysfunction was associated with reduced mitochondrial mass and ATP production. UA also decreased aconitase-2 activity and lowered enoyl CoA hydratase-1 expression. Hyperuricemic rats showed increased mitDNA damage in association with higher levels of intrarenal UA and oxidative stress.

CONCLUSIONS:

UA-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP. These studies provide additional evidence for a deleterious effect of UA on vascular function that could be important in the pathogenesis of hypertension and vascular disease.

• Authors: Laura Gabriela Sánchez-Lozada, Miguel A Lanaspa, Magdalena Cristóbal-García, Fernando García-Arroyo, Virgilia Soto, David Cruz-Robles, Takahiko Nakagawa, Min A Yu, Duk-Hee Kang, Richard J Johnson
• Journal: Nephron. Experimental nephrology (Nephron Exp Nephrol) Vol. 121 Issue 3-4 Pg. e71-8 ( 2012) ISSN: 1660-2129 [Electronic] Switzerland
• PMID: 23235493 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 S. Karger AG, Basel.

Chemical References

• Reactive Oxygen Species
• Uric Acid
• Adenosine Triphosphate

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Cells, Cultured
• Endothelium, Vascular (drug effects, metabolism, pathology)
• Humans
• Intracellular Fluid (drug effects, metabolism)
• Male
• Mitochondria (drug effects, metabolism, pathology)
• Oxidative Stress (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Uric Acid (toxicity)