Effects of low-density lipoprotein apheresis on plasma matrix metalloproteinase-9 and serum tissue inhibitor of metalloproteinase-1 levels in diabetic hemodialysis patients with arteriosclerosis obliterans.

Low density lipoprotein (LDL) apheresis provides both structural and physiologic improvement to the vascular wall. The purpose of this study was to determine whether LDL pheresis alters levels of plasma matrix metalloproteinase-9 (MMP-9) and serum tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). MMP-9 and TIMP-1 were measured in 30 healthy control subjects (Group A), 20 type 2 diabetic hemodialysis patients without obvious arteriosclerosis obliterans (ASO) (Group B), and 20 type 2 diabetic hemodialysis patients with ASO (Group C). Hemodialysis patients were dialyzed three times weekly with a bicarbonate dialysate. Twelve Group C patients underwent LDL apheresis once weekly for 10 weeks, and changes in plasma MMP-9 and serum TIMP-1 levels because of LDL apheresis were measured. LDL apheresis resulted in a significant decrease in total cholesterol and LDL cholesterol levels (p < 0.01). In addition, LDL apheresis improved clinical symptoms (including cold lower extremity, intermittent claudication, and leg pain) and diminished the size of ulcer/necrosis in all patients. Plasma MMP-9 levels were significantly higher in Group C (76.5 +/- 14.6 ng/ml) than in Group A (31.2 +/- 8.4 ng/ml, p < 0.001) or Group B (58.5 +/- 10.8 ng/ml, p < 0.05). Serum TIMP-1 levels were significantly higher in Group C (360.5 +/- 116.5 ng/ml) than in Group A (142.5 +/- 82.5 ng/ml, p < 0.001) or Group B (254.6 +/- 92.6 ng/ml, p < 0.05). Plasma MMP-9 and serum TIMP-1 levels decreased significantly after LDL apheresis (p < 0.05). However, these levels showed little change in the remaining eight Group C patients who did not undergo LDL apheresis. The data suggested that MMP-9 and TIMP-1 are associated with ASO and that LDL apheresis is effective in reducing plasma MMP-9 and TIMP-1 levels in type 2 diabetic hemodialysis patients with ASO.