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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:306-312.)
© 1995 American Heart Association, Inc.

Articles

Apolipoprotein A-II Production Rate Is a Major Factor Regulating the Distribution of Apolipoprotein A-I Among HDL Subclasses LpA-I and LpA-I:A-II in Normolipidemic Humans

Katsunori Ikewaki; Loren A. Zech; Marie Kindt; H. Bryan Brewer, Jr; Daniel J. Rader

From the Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.

Correspondence to Daniel Rader, MD, University of Pennsylvania Medical Center, BRB-1 Rm 409, 422 Curie Blvd, Philadelphia, PA 19104-6069.

Abstract HDLs are heterogeneous in their apolipoprotein composition. Apolipoprotein (apo) A-I and apoA-II are the major proteins found in HDL and form the two major HDL subclasses: those that contain only apoA-I (LpA-I) and those that contain both apoA-I and apoA-II (LpA-I:A-II). Substantial evidence indicates that these two subclasses differ in their in vivo metabolism and effect on atherosclerosis, with LpA-I the more specifically protective subfraction against atherosclerosis. The purpose of this study was to investigate the effect of apoA-I and apoA-II production and catabolism on plasma LpA-I and LpA-I:A-II levels. Fifty normolipidemic subjects (those with HDL cholesterol levels in the top and bottom tenth percentiles were excluded) underwent kinetic studies with radiolabeled apoA-I and apoA-II, and the kinetic parameters of apoA-I and apoA-II were correlated with LpA-I and LpA-I:A-II levels. ApoA-I levels were strongly correlated with apoA-I residence times and less strongly correlated with apoA-I production rates. In contrast, apoA-II levels were correlated only with apoA-II production rates and not with apoA-II residence times. Levels of apoA-I in LpA-I were correlated with apoA-I residence times, whereas levels of apoA-I in LpA-I:A-II were correlated primarily with apoA-II production rates. The fraction of apoA-I in LpA-I was highly inversely correlated with apoA-II production rate (r=-.67, P<.001). In multiple regression analysis, apoA-II production rate was the most significant independent variable determining percent apoA-I in LpA-I among all the kinetic parameters. These results indicate that in normolipidemic individuals (1) apoA-I levels are regulated primarily by apoA-I catabolism and apoA-II levels by apoA-II production; (2) the rate of catabolism of apoA-I is an important factor determining LpA-I levels, while the rate of apoA-II production is the major determinant of the amount of apoA-I in LpA-I:A-II; and (3) the rate of apoA-II production is a major factor determining the distribution of apoA-I between LpA-I and LpA-I:A-II, thereby possibly modulating susceptibility to atherosclerosis in humans.

Key Words: apoA-I • apoA-II • kinetics • radiotracer • HDLs

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