Abstract

Prebeta-1 HDL is a molecular species of plasma HDL of approximately 67 kDa mass that contains apolipoprotein A-I, phospholipids, and unesterified cholesterol. It participates in a cyclic process involved in the retrieval of cholesterol from peripheral tissues. In this cycle, unesterified cholesterol from cells is incorporated into prebeta-1 HDL, providing a substrate for esterification of cholesterol by lecithin:cholesterol acyltransferase. Prebeta-1 HDL then becomes incorporated into larger HDL species of alpha mobility as esterification proceeds and is regenerated during the transfer of cholesteryl esters from alpha HDL particles to acceptor lipoproteins. Thus the steady state level of prebeta-1 HDL in plasma reflects the relative efficiencies of the major metabolic processes involved in its generation and removal. We have used an isotope dilution technique to measure prebeta-1 HDL levels in the plasmas of 136 normolipidemic individuals (46 M, 90 F). The mean absolute concentration of prebeta-1 HDL as apolipoprotein A-I was 68 ± 40 μg/ml for women, and 84 ± 49 m/ml for men. Prebeta-1 HDL represented 5.5 ± 3.3% of total apolipoprotein A-I in women, and 7.2 ± 4.0% in men. The distributions of both absolute and percent prebeta-1 HDL are highly asymmetric, with skew toward higher values. However, the skew appears not to be attributable to either plasma cholesterol or triglyceride levels which are also skewed in population samples. The percent prebeta-1 HDL was negatively correlated with HDL cholesterol levels (P < 0.0001), whereas absolute levels of prebeta-1 HDL were positively correlated with apolipoprotein A-I and negatively correlated with HDL cholesterol (P, for both, < 0.0001). Multiple linear regression analysis revealed effects of age and gender, but no association with lipoprotein fractions other than HDL. Lower levels of prebeta-1 HDL were associated with female gender in all models.—O'Connor, P. M., B. R. Zysow, S. A. Schoenhaus, B. Y. Ishida, S. T. Kunitake, J. M. Naya-Vigne, P. N. Duchateau, R. F. Redberg, S. J. Spencer, S. Mark, M. Mazur, D. C. Heilbron, R. B. Jaffe, M. J. Malloy, and J. P. Kane. Prebeta-1 HDL in plasma of normolipidemic individuals: influences of plasma, age, and gender.

Highlights

  • Prebeta-1 high density lipoproteins (HDL) is a molecular species of plasma HDL of approximately 67 kDa mass that contains apolipoprotein A-I, phospholipids, and unesterified cholesterol

  • The potential predictors of the percentage of prebeta and absolute prebeta-1 HDL were the absolute level of apoA-I, triglycerides, HDL cholesterol, low density lipoproteins (LDL)

  • A large mass of triglycerides in plasma, reflecting increased levels of very low density lipoproteins (VLDL) or chylomicrons, would be expected to provide an entropic sink, favoring the transfer of cholesteryl esters, leading to increased formation of prebeta-1 HDL. This is consistent with findings in compound transgenic animals with hypertriglyceridemia due to overexpression of human apolipoprotein C-III in which the addition of the human cholesteryl ester transfer protein (CETP) gene resulted in depletion of cholesteryl esters in HDL [32]

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Summary

Introduction

Prebeta-1 HDL is a molecular species of plasma HDL of approximately 67 kDa mass that contains apolipoprotein A-I, phospholipids, and unesterified cholesterol. It participates in a cyclic process involved in the retrieval of cholesterol from peripheral tissues. The mean absolute concentration of prebeta-1 HDL as apolipoprotein A-I was 68 Ϯ 40 ␮g/ml for women, and 84 Ϯ 49 m/ml for men. Prebeta-1 HDL represented 5.5 Ϯ 3.3% of total apolipoprotein A-I in women, and 7.2 Ϯ 4.0% in men. The distributions of both absolute and percent prebeta HDL are highly asymmetric, with skew toward higher values.

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