Lovastatin reduces expression of the combined adhesion and scavenger receptor CD36 in human monocytic cells.
The thrombospondin and collagen receptor CD36 was recently found to function, also, as a dominating scavenger receptor for oxidized low-density lipoproteins (oxLDL). Thus, CD36 might be a key factor in monocyte adhesion and foam cell formation. We, therefore, studied CD36 expression in monocytic cells under conditions of cholesterol depletion and overload. Human monocytic U937 cells were cultured under control conditions and in the presence of lovastatin, native, and oxLDL. The expression of lipoprotein receptors was measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and fluorescence-activated cell sorting (FACS). In sharp contrast to the feedback-controlled ApoB100 specific receptor for native low-density lipoprotein (LDL-R), CD36 expression was significantly reduced by lovastatin in a dose-dependent manner, both at the RNA and protein level, resulting in decreased cellular oxLDL binding. The addition of mevalonate completely reversed lovastatin effects, whereas excess LDL was only partially effective. Similarly to native LDL, oxLDL reduced LDL-R transcription, but did not affect CD36 transcription. CD36 protein surface expression fell, however, due to internalization of CD36 loaded with oxLDL. In summary, monocytic expression of CD36, in contrast to the native LDL-R, is reduced by cholesterol synthesis inhibition and not by feedback inhibition from substrate overexposure. CD36 suppression is a new pharmacological action of lovastatin that may contribute to its clinical benefit by attenuating monocyte adhesion and foam cell formation, key steps in atherosclerosis.
Pietsch
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Institut für Prophylaxe Der Kreislaufkrankheiten, Ludwig-Maximilians-Universität München, Germany.
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Lorenz
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D001667:Binding, Competitive; D018955:CD36 Antigens; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology*; D008565:Membrane Proteins; D009000:Monocytes / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects; D011971:Receptors, Immunologic / Q000187:drug effects*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D018955:CD36 Antigens; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D008148:Lovastatin