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

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

Research output: Contribution to journalArticlepeer-review

171 Scopus citations

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.

Original languageEnglish
Pages (from-to)e71-e78
JournalNephron - Experimental Nephrology
Volume121
Issue number3-4
DOIs
StatePublished - Feb 2013

Keywords

  • Endothelial dysfunction
  • Mitochondria
  • Nitric oxide
  • Uric acid

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