title: Uric acid-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP concentrations.
abstract: OBJECTIVE
  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.affiliation: Laboratory of Renal Physiopathology and Nephrology Department, Instituto Nacional de Cardiología Ignacio Chavez, Mexico City, Mexico. lgsanchezlozada@gmail.com
authors.forename: Laura Gabriela
authors.initials: LG
authors.lastname: Sánchez-Lozada
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Lanaspa
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cristóbal-García
authors.forename: Fernando
authors.initials: F
authors.lastname: García-Arroyo
authors.forename: Virgilia
authors.initials: V
authors.lastname: Soto
authors.forename: David
authors.initials: D
authors.lastname: Cruz-Robles
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Min A
authors.initials: MA
authors.lastname: Yu
authors.forename: Duk-Hee
authors.initials: DH
authors.lastname: Kang
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014527:Uric Acid / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D014527:Uric Acid; D000255:Adenosine Triphosphate