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Nephron Exp Nephrol. 2012;121(3-4):e71-8. doi: 10.1159/000345509. Epub 2012 Dec 7.

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

Author information

1
Laboratory of Renal Physiopathology and Nephrology Department, Instituto Nacional de Cardiología Ignacio Chavez, Mexico City, Mexico. lgsanchezlozada@gmail.com

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.

PMID:
23235493
PMCID:
PMC3656428
DOI:
10.1159/000345509
[Indexed for MEDLINE]
Free PMC Article

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