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J Clin Invest. May 1979; 63(5): 858–867.
PMCID: PMC372026

Effects of Nicotinic Acid Therapy on Plasma High Density Lipoprotein Subfraction Distribution and Composition and on Apolipoprotein A Metabolism

Abstract

This report describes the effects of pharmacologic doses (3 g/d) of nicotinic acid on the plasma distribution and chemical composition of the high density lipoprotein (HDL) subfractions HDL2 and HDL3 and examines the influence of the drug on the metabolism of the major HDL apoproteins, apolipoproteins A-I (ApoA-I) and A-II (Apo-II).

The drug lowered plasma cholesterol (15%, P < 0.05) and triglyceride (27%, P < 0.01); the former effect a result of a fall in the amount of cholesterol associated with very low density lipoproteins (31%, P < 0.02) and low density lipoproteins (36%, P < 0.02). Conversely, it raised plasma HDL cholesterol (23%, P < 0.05) and increased (by 345%) the plasma HDL2:HDL3 ratio. The latter derived from an absolute increment (646%) in circulating HDL2, coupled with a fall (47%) in HDL3. This change was not associated with major alterations in the overall cholesterol (free and esterified), triglyceride, phospholipid, or protein content of the subfractions; however, it was accompanied by substantial changes in their protein composition. In particular, the molar ratio of ApoA-I:ApoA-II in HDL3 declined from 2.7:1 to 2.1:1 during nicotinic acid treatment.

Significant perturbations of ApoA-I and ApoA-II metabolism accompanied the drug-induced HDL subfraction redistribution. Specifically, the plasma concentration of ApoA-I rose by 7% (P < 0.05) because of a decrease in its fractional catabolic rate. Moreover, whereas before treatment 6 and 94% of the plasma ApoA-I circulated with HDL2 and HDL3, after commencement of nicotinic acid therapy this distribution became 49 and 51% in HDL2 and HDL3, respectively. ApoA-II was found mainly in HDL3, both before and during nicotinic acid treatment. Administration of the drug caused a 14% reduction in its plasma concentration (P < 0.05), which derived principally from a fall (22%, P < 0.01) in its synthetic rate.

These data suggest that the effects of nicotinic acid on the HDL subfraction distribution may be mediated via (a) net transfer of ApoA-I from HDL3 to HDL2 and (b) a reduction in ApoA-II synthesis. Our present understanding of the association between HDL and atherosclerosis indicates that such changes may have prophylactic value in the prevention of coronary artery disease.

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Selected References

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