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

被引：70

作者：

IKEWAKI, K ^{[1
]}

ZECH, LA ^{[1
]}

KINDT, M ^{[1
]}

BREWER, HB ^{[1
]}

RADER, DJ ^{[1
]}

机构：

[1] NHLBI, MOLEC DIS BRANCH, BETHESDA, MD 20892 USA

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 1995年 / 15卷 / 03期

关键词：

APOA-I; APOA-II; KINETICS; RADIOTRACER; HDLS;

D O I：

10.1161/01.ATV.15.3.306

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

HDLs are heterogeneous in their apolipoprotein composition. Apolipoprotein (ape) 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.

引用

页码：306 / 312

页数：7

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