Systemic levels of MMP2/TIMP2 and cardiovascular risk in CAPD patients.
OBJECTIVE
Matrix metalloproteinases (MMPs), their inhibitors (TIMPs), oxidative stress (SOX) and kynurenine (KYN) pathway have been postulated in cardiovascular disease (CVD) progression. We hypothesized the possible association between the MMP/TIMP system, KYNs and CVD prevalence in continuous ambulatory peritoneal dialysis (CAPD) patients.


METHODS
We assessed MMP-2, MMP-9, TIMP-1, TIMP-2, KYN and its metabolite - quinolinic acid (QA), and SOX marker - Cu/Zn superoxide dismutase (Cu/Zn SOD) levels in CAPD patients both with and without CVD and healthy controls.


RESULTS
MMP-2, TIMP-2, Cu/Zn SOD, KYN and QA were significantly higher in CAPD patients with CVD than in patients without CVD and controls. MMP-2 and TIMP-2 were positively correlated with QA and Cu/Zn SOD levels, and the strong association was between MMP-2 and TIMP-2 levels. Multiple regression analyses identified Cu/Zn SOD, TIMP-2, QA and QA/KYN ratio as the factors independently associated with MMP-2, whereas MMP-2 and Cu/Zn SOD were independent variables affecting TIMP-2 levels.


CONCLUSIONS
MMP-2 and TIMP-2 concentrations were higher in CAPD patients with CVD than in patients without CVD and healthy controls. Upregulation of the MMP-2/TIMP-2 system was associated with QA levels and increased oxidative status, suggesting the connection between KYN pathway activation, arterial remodeling and CVD prevalence in uremic patients on CAPD treatment.
Pawlak
Krystyna
K
Department of Monitored Pharmacotherapy, Medical University, Bialystok, Poland. dariuszpawlak @ poczta.onet.pl
Tankiewicz
Janina
J
Mysliwiec
Michal
M
Pawlak
Dariusz
D
D000328:Adult; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects*; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012680:Sensitivity and Specificity; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*
D015415:Biomarkers; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2