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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:384-392.)
© 1999 American Heart Association, Inc.

Original Contributions

Cholesterol or Triglyceride Loading of Human Monocyte-Derived Macrophages by Incubation With Modified Lipoproteins Does Not Induce Tissue Factor Expression

Mark M. E. D. van den Eijnden; Jacqueline T. van Noort; Leny Hollaar; Arnoud van der Laarse; Rogier M. Bertina

From the Hemostasis and Thrombosis Research Center, Departments of Hematology (M.M.E.D.v.d.E., J.T.v.N., R.M.B.) and Cardiology (L.H., A.v.d.L.), Leiden University Medical Center (University Hospital), Leiden, the Netherlands.

Correspondence to M.M.E.D. van den Eijnden, Hemostasis and Thrombosis Research Center, Department of Hematology, Leiden University Medical Center (University Hospital), Bldg 1, C2-R, PO Box 9600, 2300 RC Leiden, the Netherlands. E-mail rbertina{at}hematology.azl.nl

Abstract—Macrophages/foam cells localized in cholesterol- and triglyceride-rich regions of atherosclerotic plaques express high levels of tissue factor (TF), the essential cofactor and receptor of factor VIIa. It is not clear whether modified lipoproteins, for which several agonistic effects on macrophages have been described, are independent stimuli of TF expression in these cells. Therefore, we studied the effect of short-term (1 day) and long-term (4 to 7 days) incubation of human monocyte-derived macrophages cultured in suspension with modified and native LDLs or VLDLs on the expression of TF mRNA, antigen, and activity. We used native LDL or VLDL, moderately oxidized LDL or VLDL, severely oxidized LDL or VLDL, acetylated LDL, and ß-VLDL at a protein concentration of 100 µg/mL. Cholesterol loading occurred within 9 hours after the addition of acetylated LDL and continued during long-term incubation. Incubation of severely oxidized LDL for 7 days resulted in a slight increase in cholesterol content. Triglyceride loading was observed during short-term and long-term incubation with native and modified VLDLs. Neither cholesterol nor triglyceride loading resulted in expression of TF. Bacterial LPS still could induce TF expression in lipid-laden macrophages. Our results show that incubation with modified lipoproteins or lipid loading does not lead to TF expression in monocyte-derived macrophages cultured in suspension. This suggests that induction of TF expression in foam cells in the atherosclerotic lesion is triggered by additional or other components.

Key Words: monocyte-derived macrophages • lipoproteins • lipopolysaccharide • tissue factor • atherosclerosis

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