Systemic levels of MMP2/TIMP2 and cardiovascular risk in CAPD patients

摘要

Background/Aims: 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.