UPTAKE OF EXOGENOUS FREE-CHOLESTEROL INDUCES UP-REGULATION OF TISSUE FACTOR EXPRESSION IN HUMAN MONOCYTE-DERIVED MACROPHAGES

被引：85

作者：

LESNIK, P ^{[1
]}

ROUIS, M ^{[1
]}

SKARLATOS, S ^{[1
]}

KRUTH, HS ^{[1
]}

CHAPMAN, MJ ^{[1
]}

机构：

[1] NHLBI,EXPTL ATHEROSCLEROSIS SECT,BETHESDA,MD 20892

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1992年 / 89卷 / 21期

关键词：

THROMBOSIS; ATHEROSCLEROSIS;

D O I：

10.1073/pnas.89.21.10370

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Lipid-laden macrophages present as foam cells may contribute to the hyperthrombotic state of human atherosclerotic lesions by the production of tissue factor (TF). We investigated the effect of exogenous nonlipoprotein cholesterol on the expression of TF by human monocyte-derived macrophages in culture. Nonlipoprotein cholesterol at 50 mug/ml increased TF activity 4-fold; TF induction was dose- and time-dependent. Expression of TF activity was positively correlated with the free cholesterol content of monocyte-derived macrophages, was increased upon inhibition of cholesterol esterification, and reflected de novo synthesis of TF protein. TF expression in cholesterol-loaded macrophages remained sensitive to stimulation (almost-equal-to 12-fold) by bacterial lipopolysaccharide, indicating that intracellular free cholesterol and lipopolysaccharide act by distinct mechanisms in inducing TF procoagulant activity. Our results suggest that loading human monocyte-derived macrophages with free cholesterol induces upregulation of TF expression, thereby contributing to thrombus formation at sites of plaque rupture.

引用

页码：10370 / 10374

页数：5

共 26 条

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