| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Lovastatin Decreases the Receptor-Mediated Degradation of Acetylated and Oxidized LDLs in Human Blood Monocytes During the Early Stage of Differentiation Into Macrophages
From the Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Ludwig-Maximilians-Universität, München, Germany.
Correspondence to N. Hrboticky, Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Ludwig-Maximilians-Universität, Pettenkoferstraße 9, 80336 München, Germany. E-mail ninahrboticky{at}klp.med.uni-muenchen.de
Abstract—3-Hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors are used therapeutically to upregulate the LDL receptor-mediated removal of plasma cholesterol by the liver. Several lines of evidence indicate that these drugs also exert direct effects on the metabolism of native and modified LDL in extrahepatic cells. We studied the effects of lovastatin (LOV) on the degradation of native, acetylated, and oxidized LDL, and on levels of mRNA encoding for the LDL, types I and II class A macrophage scavenger, and CD36 receptors in human blood monocytes at different stages of their maturation into adherent macrophages. LOV (10 µmol/L) reduced the degradation of acetylated LDL when added to freshly isolated cells cultured for 2 (81±4% of control, P<0.05) and 5 (76±6%, of control, P<0.05) days. The degradation of oxidized LDL was also reduced in cells treated with LOV for 2 days after seeding (51±3% of control, P<0.001) but not in 5-day-old cells. LOV had no significant effect on the degradation of either acetylated or oxidized LDL when added to fully matured macrophages allowed to differentiate under control conditions for 7 days before incubations with 10 µmol/L LOV for an additional 2 days. In contrast, LOV increased the degradation of native LDL in these cells at all 3 stages of cell differentiation. LOV also reduced class A types I and II macrophage scavenger receptor and CD36 mRNA levels in 2- and 5-day-old cells but not in the more mature macrophages. These data suggest that 3-hydroxy-3-methylglutaryl–coenzyme A inhibitors may reduce the expression and function of the class A types I and II macrophage scavenger receptor and CD36 in monocytes, during the early stages of their differentiation into adherent macrophages. These effects, if operative in vivo, may slow down the development of the atherosclerotic plaque and thus contribute to the beneficial effects of these drugs.
Key Words: scavenger receptor • LDL receptor • acetylated LDL • oxidized LDL • CD36 • 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitor • monocyte
This article has been cited by other articles:
 |
|
 |
|
  I. Sethy-Coraci, L. W. Crock, and S. C. Silverstein PAF-receptor antagonists, lovastatin, and the PTK inhibitor genistein inhibit H2O2 secretion by macrophages cultured on oxidized-LDL matrices J. Leukoc. Biol., November 1, 2005; 78(5): 1166 - 1174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Antonov, F. D. Kolodgie, D. H. Munn, and R. G. Gerrity Regulation of Macrophage Foam Cell Formation by {alpha}V{beta}3 Integrin: Potential Role in Human Atherosclerosis Am. J. Pathol., July 1, 2004; 165(1): 247 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Han, X. Zhou, T. Yokoyama, D. P. Hajjar, A. M. Gotto Jr, and A. C. Nicholson Pitavastatin Downregulates Expression of the Macrophage Type B Scavenger Receptor, CD36 Circulation, February 17, 2004; 109(6): 790 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Draude and R. L. Lorenz TGF-beta 1 downregulates CD36 and scavenger receptor A but upregulates LOX-1 in human macrophages Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1042 - H1048. [Abstract] [Full Text] [PDF]
|
|