Bezafibrate Increases Preβ1-HDL at the Expense of HDL _2b in Hypertriglyceridemia

Abstract

Abstract-Pre␤1-high density lipoprotein (pre␤1-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 pre␤1-HDL at the expense of HDL 2 . To answer this question, we determined the apolipoprotein A-I (apoA-I) distribution in 20 hypertriglyceridemics (triglyceridesϾ2.26 mmol/L) and 20 sex-matched normolipidemics by native 2-dimensional gel electrophoresis. At baseline, pre␤1-HDL was 70% higher in hypertriglyceridemics than in normolipidemics (123.5Ϯ49.

Analytical performance of a sandwich enzyme immunoassay for preβ1-HDL in stabilized plasma

“…Fresh plasma was separated in the first dimension by electrophoresis on 0.75% agarose gels, and then in the second dimension by electrophoresis on gradient (2% to 15%) polyacrylamide gels (14,21,(25)(26)(27)(28). The separated HDL subfractions in the polyacrylamide gels were then electroblotted onto nitrocellulose membranes.…”

“…This property of pre ␤ 1-HDL is similar to that of reconstituted lipid-poor HDL (20), an experimental model of nascent HDL. Although pre ␤ 1-HDL comprises only a small proportion of the total apoA-I in healthy subjects (14,(21)(22)(23), its level changes significantly in coronary artery disease (14,24), obesity (23), and hyperlipidemia (21,(25)(26)(27), as well as in patients treated with lipid-lowering therapies (21,27). Pre ␤ 1-HDL concentrations are currently measured in a limited number of clinical laboratories by native twodimensional (2D)-gel electrophoresis (14,(23)(24)(25)(26)(27).…”

Effects of Established Hypolipidemic Drugs on HDL Concentration, Subclass Distribution, and Function

“…A number of studies have shown that treatment with fibrates causes a shift of HDL from large to small particles in low HDL (Franceschini et al 2007;Otvos et al 2006), hypertriglyceridemic (Miida et al 2000;Sasaki et al 2002), and hypercholesterolemic (Franceschini et al 1989) patients. These effects could be explained by the fibrate-induced increase in hepatic lipase activity (Miida et al 2000;Patsch et al 1984).…”

“…These effects could be explained by the fibrate-induced increase in hepatic lipase activity (Miida et al 2000;Patsch et al 1984). In addition, bezafibrate has been shown to increase small discoidal preβ1-HDL particles in hypertriglyceridemic patients (Miida et al 2000).…”

“…These effects could be explained by the fibrate-induced increase in hepatic lipase activity (Miida et al 2000;Patsch et al 1984). In addition, bezafibrate has been shown to increase small discoidal preβ1-HDL particles in hypertriglyceridemic patients (Miida et al 2000). The analysis of HDL subclasses by 2-D electrophoresis in the large cohort of the VA-HIT trial confirmed that gemfibrozil treatment is associated with a decrease in large (α-1 and α-2) HDL and with an increase in the small, lipid-poor HDL particles ).…”