Apolipoprotein A and B (Sf 100-400) metabolism during bezafibrate therapy in hypertriglyceridemic subjects.

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Abstract

This study describes the effects of bezafibrate, an analogue of clofibrate, on the plasma lipid and lipoprotein profiles of 11 hypertriglyceridemic subjects and on their metabolism of apolipoproteins A-I, A-II, and B. The major action of the drug was to lower plasma triglyceride (by 58%; P less than 0.01). This was accompanied by a reduction in the level of very low density lipoprotein apoprotein B (Svedberg units of flotation [Sf] 60-400), whose mean residence time in the plasma fell threefold (from 3.4 to 1.0 h). Synthesis of the B protein in this fraction was not significantly altered, so the drug acts to accelerate the transit of very low density lipoprotein particles down the delipidation cascade. The metabolism of very low density lipoprotein remnant apoprotein B (Sf 12-100) changed little in response to treatment, although we detected a 30% increment (P less than 0.05) in the plasma concentration of this fraction. The mean residence time of these remnant particles in the plasma did not correlate with that of Sf 100-400 very low density lipoprotein apoprotein B, nor was this parameter altered by the drug. The most consistent and significant perturbation seen in the Sf 0-12 fraction (low density lipoprotein) was a reduction in the fractional catabolism of its apoprotein B moiety (26%; P less than 0.05). In those subjects who were grossly hypertriglyceridemic and who responded well to treatment, the level of this protein rose substantially owing to a combined increase in its synthesis and a reduction in its catabolism. In the group as a whole, high density lipoprotein cholesterol rose 13% (P less than 0.02), and detailed examination showed that this was associated with a small but significant increment in the plasma concentration of the high density lipoprotein subfraction 2. High density lipoprotein subfraction 3 also rose on the average, but this was not a consistent feature in all patients. The plasma concentrations and turnovers of the A proteins (A-I and A-II) were not significantly altered by bezafibrate therapy.

Authors

J Shepherd, C J Packard, J M Stewart, R F Atmeh, R S Clark, D E Boag, K Carr, A R Lorimer, D Ballantyne, H G Morgan