Bezafibrate increases preβ1-HDL at the expense of HDL2b in hypertriglyceridemia

Pre beta1-high density lipoprotein (pre beta1-HDL), the initial acceptor of cell-derived cholesterol, can be generated from HDL2 by hepatic lipase. Because bezafibrate elevates lipase activity, it may increase pre beta1-HDL at the expense of HDL2. 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, pre beta1-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). Pre<beta>1-HDL was positively correlated with triglyceride (r=0.624, P<0.0001). A 4-week bezafibrate treatment (400 mg daily) increased pre<beta>1-HDL by 30% (160.2+/-6415 mg/L apoA-I, P<0.05) but decreased HDL2b 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); Pre<beta>1-HDL was generated either from ultracentrifugally isolated HDL2 or from plasma during incubation with triglyceride lipase. In conclusion, bezafibrate increases pre beta1-HDL at the expense of HDL2. We speculate that such an effect might partly contribute to the antiatherogenic action of bezafibrate.