Uric acid-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular
Laura Gabriela Sánchez-Lozada1, Miguel A Lanaspa, Magdalena Cristóbal-García
1Laboratory of Renal Physiopathology and Nephrology Department, Instituto Nacional de Cardiología Ignacio Chavez, Mexico City, Mexico. lgsanchezlozada@gmail.com
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.
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