Urokinase-type plasminogen activator and metalloproteinase-2 are independently related to the carotid atherosclerosis in haemodialysis patients.
BACKGROUND
Matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs) system, and fibrinolytic system, have been implicated as important factors in atherosclerosis and vascular remodeling. However, no data are yet available on the associations between these two systems in relation to carotid atherosclerosis in hemodialysis (HD) patients.


METHODS
We compared plasma levels of MMP-2, MMP-9, TIMP-1, TIMP-2; the parameters of fibrinolytic system: tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPAR) and its soluble receptor (suPAR), plasminogen activator inhibitor-1 (PAI-1), plasmin-alpha2-antiplasmin (PAP) complexes; high sensitivity C-reactive protein (hs CRP) as a marker of inflammation and a surrogate of atherosclerotic disease-intima media thickness (IMT) in HD patients and in healthy controls.


RESULTS
The values of the uPA, suPAR, PAP, MMP-2, TIMPs, hs CRP and IMT in the patients significantly exceeded those in controls. The concentrations of MMP-9, tPA and PAI-1 were similar in both investigated groups. uPA, uPAR and PAP were positively associated with MMP-2/TIMPs system; all mentioned above parameters (except TIMP-2) and hsCRP were associated with IMT. Multivariate analysis showed that uPA, MMP-2 and age were the strong independent variables linked to IMT values in HD patients.


CONCLUSIONS
The patients on haemodialysis treatment have evidence of disordered fibrinolysis/proteolysis balance in the plasma, independently associated with IMT on multivariate analysis. These data suggest the importance of uPA and MMP-2 levels in the developing of atherosclerosis in these patients.
Pawlak
Krystyna
K
Department of Nephrology and Clinical Transplantation, Medical University, Bialystok, Poland. krystynapawlak@poczta.onet.pl
Pawlak
Dariusz
D
Myśliwiec
Michal
M
D000328:Adult; D000368:Aged; D002340:Carotid Artery Diseases / Q000097:blood / Q000209:etiology*; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000502:physiology*; D008875:Middle Aged; D015999:Multivariate Analysis; D006435:Renal Dialysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood / Q000502:physiology*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2