Hormonal and cytokine effects of uric acid.
OBJECTIVE
Current evidence supports the role of soluble uric acid as a true mediator of injury, exerting its effects through the induction of growth factors, cytokines, hormones and autacoids. In the present review, we summarize recent studies on the mechanisms involved in the uric acid deleterious effects.


RESULTS
Although uric acid is considered an antioxidant in plasma, recent clinical and epidemiological studies have found that hyperuricemia is associated with mortality and development of hypertension, cardiovascular and chronic renal diseases. Experimental studies suggest that uric acid induce its detrimental effects at the cellular level entering to vascular smooth muscle cells (VSMC) via an organic anion transport system, and followed by the activation of specific MAP kinases, nuclear transcription factors, with stimulation of COX-2, PDGF A and C chain, PDGF alpha receptor, and various inflammatory mediators, including C-reactive protein and monocyte chemoattractant protein-1. Physiologically, these effects translate into a rise of arterial pressure, VSMC hypertrophy, tubulointerstitial infiltration and glomerular hypertension in the setting of renal vasoconstriction. Uric acid also promotes endothelial dysfunction through inactivation of NO and arresting the proliferation of endothelial cells. Thus, arteriosclerosis induced by hyperuricemia may be a novel mechanism for the development of essential hypertension.


CONCLUSIONS
Soluble uric acid has important biologic roles. While it acts as an antioxidant, there is also evidence that uric acid has pro-inflammatory and proliferative effects on VSMC, and causes dysfunction of endothelial cells. These cellular mechanisms may translate into why uric acid is associated with renal and cardiovascular disease.
Sánchez-Lozada
Laura G
LG
Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Nakagawa
Takahiko
T
Kang
Duk-Hee
DH
Feig
Dan I
DI
Franco
Martha
M
Johnson
Richard J
RJ
Herrera-Acosta
Jaime
J
D000975:Antioxidants / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D033461:Hyperuricemia / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D014527:Uric Acid / Q000009:adverse effects* / Q000378:metabolism; D014652:Vascular Diseases / Q000209:etiology
D000975:Antioxidants; D014527:Uric Acid