LCAT-Dependent Conversion of Preβ1-HDL into α-Migrating HDL is Severely Delayed in Hemodialysis Patients

Abstract

Preβ1-HDL is a minor HDL subfraction that acts as an efficient initial acceptor of cell-derived free cholesterol. During 37°C incubation, plasma preβ1-HDL decreases over time due to its conversion to α-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 preβ1-HDL to α-migrating HDL is delayed in hemodialysis patients, preβ1-HDL concentrations were determined in 45 hemodialysis patients and 45 gender-matched control subjects before and after 37°C incubation with and without the LCAT inhibitor. It was found that the baseline preβ1-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 preβ1-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 preβ1-HDL levels (DR_preβ1) was the same for samples from hemodialysis patients exhibiting normal (≥1.03 mmol/L) and low HDL-cholesterol levels (32 ± 32 versus 28 ± 23% of baseline; NS). DR_preβ1 was positively correlated with LCAT activity (r = 0.617; P < 0.001). In conclusion, the LCAT-dependent conversion of preβ1-HDL to α-migrating HDL is severely delayed in hemodialysis patients. The impaired catabolism of preβ1-HDL may accelerate atherosclerosis in hemodialysis patients. E-mail: miida@med.niigata-u.ac.jp