Decreases in plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in uremic patients during hemodialysis.

Abstract

Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) play important roles in the pathophysiology of renal diseases. Imbalanced MMPs/TIMPs are implicated in the vascular alterations of uremic patients on hemodialysis (HD). We have investigated the plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 in uremic patients and the effects of a course of HD on the changes in these factors. There were 382 uremic patients on regular HD treatment and 50 healthy controls enrolled in this study. The plasma MMP-2 and MMP-9 levels were detected by gelatin zymography, and TIMP-1 and TIMP-2 concentrations were determined by ELISA assay. Significantly higher plasma MMP-2 and MMP-9 and decreased TIMP-1 in the uremic patients were detected compared with those in the controls. Therefore, there were markedly higher MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in the uremic patients. In the course of a single HD session, the plasma MMP-2 level was significantly decreased from pre-HD to post-HD. TIMP-1 concentration was significantly increased from pre-HD to post-HD. Although the HD session did not have a significant effect on the levels of plasma MMP-9 and TIMP-2, both plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios were significantly decreased from pre-HD to post-HD levels. HD session could decrease MMP-2 and increase TIMP-1 level in the circulation of uremic patients. The physiological significance of reduced MMPs/TIMPs ratio due to a single HD session is required to further validate.