LCAT-dependent conversion of Preβ1-HDL into α-migrating HDL is severely delayed in hemodialysis patients

Prebeta1-HDL is a minor HDL subtraction that acts as an efficient initial acceptor of cell-derived free cholesterol. During 37degreesC incubation, plasma prepl-HDL decreases over time due to its conversion to alpha-migrating HDL by lecithin: cholesterol acyltransferase (LCAT). This conversion may be delayed in hemodialysis patients who have decreased LCAT activity. To clarify whether LCAT-dependent conversion of prebeta1-HDL to alpha-migrating HDL is delayed in hemodialysis patients, prepl-HDL concentrations were determined in 45 hemodialysis patients and 45 gender-matched control subjects before and after 37degreesC incubation with and without the LCAT inhibitor. It was found that the baseline prebeta1-HDL concentration in hemodialysis patients was more than twice that in the controls (44.9 +/- 21.4 versus 19.8 +/- 6.7 mg/L apoAI; P < 0.001). After 2-h incubation, the LCAT-dependent decrease in prepl-HDL in hemodialysis patients was about one-third of that in the controls (30 +/- 27 versus 97 +/- 17% of baseline; P < 0.01). The LCAT-dependent rate of decrease in prebeta1-HDL levels (DRprebeta1) was the same for samples from hemodialysis patients exhibiting normal (greater than or equal to1.03 mmol/L) and low HDL-cholesterol levels (32 +/- 32 versus 28 +/- 23% of baseline; NS). DRPprebeta1 was positively correlated with LCAT activity (r = 0.617; P < 0.001). In conclusion, the LCAT-dependent conversion of pre beta 1-HDL to a-migrating HDL is severely delayed in hemodialysis patients. The impaired catabolism of pre beta 1-HDL may accelerate atherosclerosis in hemodialysis patients.