Uptake of exogenous free cholesterol induces upregulation of tissue factor expression in human monocyte-derived macrophages.
AUTOR(ES)
Lesnik, P
RESUMO
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 micrograms/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 (approximately 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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=50340Documentos Relacionados
- Lipoprotein lipase secretion by human monocyte-derived macrophages.
- Substance P augments tumor necrosis factor release in human monocyte-derived macrophages.
- Growth kinetics of human cytomegalovirus are altered in monocyte-derived macrophages.
- Fate of Chlamydia trachomatis in human monocytes and monocyte-derived macrophages.
- Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-derived macrophages.
