Bezafibrate Increases Preβ1-HDL at the Expense of HDL 2b in Hypertriglyceridemia

Abstract

Abstract —Preβ1-high density lipoprotein (preβ1-HDL), the initial acceptor of cell-derived cholesterol, can be generated from HDL 2 by hepatic lipase. Because bezafibrate elevates lipase activity, it may increase preβ1-HDL at the expense of HDL 2 . To answer this question, we determined the apolipoprotein A-I (apoA-I) distribution in 20 hypertriglyceridemics (triglycerides>2.26 mmol/L) and 20 sex-matched normolipidemics by native 2-dimensional gel electrophoresis. At baseline, preβ1-HDL was 70% higher in hypertriglyceridemics than in normolipidemics (123.5±49.9 versus 72.5±34.1 mg/L apoA-I, P <0.01). Preβ1-HDL was positively correlated with triglyceride ( r =0.624, P <0.0001). A 4-week bezafibrate treatment (400 mg daily) increased preβ1-HDL by 30% (160.2±64.5 mg/L apoA-I, P <0.05) but decreased HDL 2b by 31% (from 188.8±94.9 to 129.3±78.7 mg/L apoA-I, P <0.05). Hepatic lipase activity increased by 24% ( P <0.005). Preβ1-HDL was generated either from ultracentrifugally isolated HDL 2 or from plasma during incubation with triglyceride lipase. In conclusion, bezafibrate increases preβ1-HDL at the expense of HDL 2 . We speculate that such an effect might partly contribute to the antiatherogenic action of bezafibrate.