Serum matrix metalloproteinase-2 and increased oxidative stress are associated with carotid atherosclerosis in hemodialyzed patients

Abstract

Matrix metalloproteinases (MMPs)/their inhibitors (TIMPs) system and elevated oxidative stress (SOX) have been implicated as important factors in atherosclerosis and vascular remodeling. The aim of the present study was to investigate whether MMPs/TIMPs system is associated with SOX in hemodialyzed (HD) patients. We compared the serum levels of metalloproteinases and their inhibitors, markers of SOX, inflammation and atherosclerosis between HD patients ( n = 40) with and without cardiovascular disease (CVD) and controls ( n = 20). Cu/Zn superoxide dismutase (Cu/Zn SOD) were elevated (all p < 0.001), whereas total lipid peroxide levels were similar in HD patients and controls. The autoantibodies against oxidized LDL (OxLDL-Ab) levels were increased only in patients with CVD ( p < 0.05). Intima media thickness (IMT) in both CVD and in patients without CVD significantly exceeded those in the control ( p < 0.001 and p < 0.01, respectively). Serum pre-HD values of MMP-2, TIMP-1 and TIMP-2 were significantly increased in HD patients, especially in the CVD group (all p < 0.001), and they were associated with those of Cu/Zn SOD, IMT and CVD prevalence. Multiple regression analysis showed that MMP-2, Cu/Zn SOD levels and age independently and significantly predicted elevated IMT in HD patients. Our results suggest the association between SOX and the MMPs/TIMPs system in HD patients, which could represent one of the mechanisms involved in the progression of atherosclerosis in this population.