Impaired antioxidant action of high density lipoprotein in patients with type 1 diabetes with normoalbuminuria and microalbuminuria.

AIMS: Patients with type 1 diabetes, in the absence of chronic complications, have serum concentrations of high density lipoprotein cholesterol (HDL-C) similar to the general population. However, their HDL particles may be dysfunctional. We aimed to evaluate the antioxidant effect of HDL2 and HDL3 obtained from Caucasian males with type 1 diabetes with normoalbuminuria and microalbuminuria. METHODS: Twenty Caucasian men with type 1 diabetes (10 with normoalbuminuria and 10 with microalbuminuria) and 10 healthy Caucasian men participated in the study. Lipoproteins were obtained by density gradient ultracentrifugation. The antioxidant effect of HDL was assessed by measuring lipid hydroperoxide (LOOH) concentration after 3h of pooled LDL oxidation catalyzed by 5µM CuSO4 in the absence or presence of HDL2 or HDL3. RESULTS: The control, normoalbuminuria, and microalbuminuria groups had similar HDL-C concentration and estimated glomerular filtration rate. Glycemic control was similar between diabetes groups (HbA1c 8.1±0.9% and 8.3±0.7%, P=0.70), but estimated glucose disposal rate was lower in patients with microalbuminuria (8.0±0.6 and 4.5±1.1mg/kg/min, P<0.01). The relative antioxidant effect of HDL2 from control, normoalbuminuria, and microalbuminuria groups were 92.8±2.4%, 85.4±1.7%, and 74.2±4.6%, respectively (P<0.01), and the HDL3 effect were 95.0±2.2%, 86.4±4.4%, and 75.3±4.2%, respectively (P<0.01). CONCLUSION: Both HDL2 and HDL3 inhibited LOOH formation in copper-catalyzed oxidation of LDL in vitro. Overall, this antioxidant effect was lower in Caucasian men with type 1 diabetes, and was further compounded in those with microalbuminuria.

HDL2 can inhibit further oxidative modification of partially oxidized LDL.

AIM: To investigate whether HDL(2) can inhibit further oxidative modification of partially oxidized LDL (ox-LDL) by interrupting the chain oxidation reaction after lipid hydroperoxides (LOOH) formation. METHODS: Following incubation of LDL 400 microg protein/mL phosphate-buffered saline with Cu(2+) for 1.75 h (defined as 0 min), incubation was continued after adding HDL(2) 200 microg protein/mL or HDL(2) 800 microg protein/mL to give both ox-LDL+HDL(2) 200 microg protein/mL or ox-LDL+HDL(2) 800 microg protein/mL. As a control, ox-LDL 200 microg protein/mL and native LDL were prepared. Each sample was subjected to agarose gel electrophoresis and the LOOH in each sample was measured. RESULTS: When the electrophoretic mobility of native LDL was designated 1, the relative electrophoretic mobility (REM) of ox-LDL increased significantly over time. The REMs of ox-LDL+HDL(2) 800 microg protein/mL from 10 min to 9 h were significantly lower than the REM of ox-LDL at the respective times (p<0.01). LOOH of ox-LDL+HDL(2) 800 microg protein/mL at 1, 3, 6 and 9 h was significantly higher than LOOH in ox-LDL at the respective times (p<0.01). The results of ox-LDL+HDL(2) 200 microg protein/mL were almost the same but to a lesser extent than the results of ox-LDL+HDL(2) 800 microg protein/mL. CONCLUSION: The present findings suggest that HDL(2) can inhibit further oxidative modification of partially oxidized LDL by interrupting the chain oxidation reaction after LOOH formation in a concentration-dependent manner.