Urotensin II and biomarkers of endothelial activation and atherosclerosis in end-stage renal disease.
BACKGROUND
Urotensin II (UTN), a cyclic undecapeptide widely distributed in various organs and tissues, is found in high concentration in atheromatous lesions. Because UTN accumulates in patients with chronic renal failure, the association between plasma UTN and biomarkers of atherosclerosis and endothelial activation needs to be better understood.


METHODS
We tested by a robust statistical approach (Holm method) the association between plasma UTN and biomarkers of atherosclerosis and endothelial activation in a population of 191 patients undergoing chronic hemodialysis.


RESULTS
Plasma UTN was significantly higher in patients with end-stage renal disease (median: 6.5 ng/mL) than in healthy subjects (median: 3.1 ng/mL) (P < .001), and in both patients and control subjects it was independent of age and sex. Interestingly, UTN was inversely related to fibrinogen (r = -0.50, P < .004), intracellular adhesion molecule-1 (r = -0.24, P < .004) and with NO synthesis inhibitor asymmetric dimethyl-arginine (r = -0.40, P < .004). These links were paralleled by direct correlations with albumin (r = 0.21, P < .006) and with transforming growth factor-beta1 (TGFbeta1) (r = 0.36, P < .004). Of note, on multiple regression analysis, these associations remained highly significant also after data adjustment for potential confounders.


CONCLUSIONS
The inverse links between UTN with biomarkers of atherosclerosis and endothelial activation suggest that downregulation of UTN may be a counter-regulatory response aimed at mitigating cardiovascular damage or that UTN itself is a protective factor.
Mallamaci
Francesca
F
CNR-IBIM, Institute of Biomedicine, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension and Division of Nephrology, Dialysis and Transplantation, Reggio Calabria, Italy.
Cutrupi
Sebastiano
S
Pizzini
Patrizia
P
Tripepi
Giovanni
G
Zoccali
Carmine
C
D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D050197:Atherosclerosis / Q000097:blood* / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012307:Risk Factors; D014579:Urotensins / Q000097:blood*
D015415:Biomarkers; D014579:Urotensins; D018799:Intercellular Adhesion Molecule-1; C018524:N,N-dimethylarginine; C029677:urotensin II; D001120:Arginine