title: Role of macrophage-derived lipoprotein lipase in lipoprotein metabolism and atherosclerosis.
abstract: Lipoprotein lipase (LPL) synthesis by macrophages is upregulated in early atherogenesis, implicating the possible involvement of LPL in plaque formation. However, it is still unclear whether macrophage-derived LPL displays a proatherosclerotic or an antiatherosclerotic role in atherosclerotic lesion development. In this study, the role of macrophage-derived LPL on lipid metabolism and atherosclerosis was assessed in vivo by transplantation of LPL-deficient (LPL-/-) and wild-type (LPL+/+) bone marrow into C57BL/6 mice. Eight weeks after bone marrow transplantation (BMT), serum cholesterol levels in LPL-/--->C57BL/6 mice were reduced by 8% compared with those in LPL+/+-->C57BL/6 mice (P:<0.05, n=16), whereas triglycerides were increased by 33% (P:<0.05, n=16). Feeding the mice a high-cholesterol diet increased serum cholesterol levels in LPL-/--->C57BL/6 and LPL+/+-->C57BL/6 mice 5-fold and 9-fold, respectively, resulting in a difference of approximately 50% (P:<0. 01) after 3 months on the diet. No effects on triglyceride levels were observed under these conditions. Furthermore, serum apolipoprotein E levels were reduced by 50% in the LPL-/--->C57BL/6 mice compared with controls under both dietary conditions. After 3 months on a high-cholesterol diet, the atherosclerotic lesion area in LPL-/--->C57BL/6 mice was reduced by 52% compared with controls. It can be concluded that macrophage-derived LPL plays a significant role in the regulation of serum cholesterol, apolipoprotein E, and atherogenesis, suggesting that specific blockade of macrophage LPL production may be beneficial for decreasing atherosclerotic lesion development.
authors.affiliation: Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Sylvius Laboratories, Leiden University, Leiden, The Netherlands. M.Eck@LACDR.LeidenUniv.nl
authors.forename: M
authors.initials: M
authors.lastname: Van Eck
authors.forename: R
authors.initials: R
authors.lastname: Zimmermann
authors.forename: P H
authors.initials: PH
authors.lastname: Groot
authors.forename: R
authors.initials: R
authors.lastname: Zechner
authors.forename: T J
authors.initials: TJ
authors.lastname: Van Berkel
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000097:blood; D001161:Arteriosclerosis / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary; D005260:Female; D006801:Humans; D007455:Iodine / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008111:Liver Function Tests; D008264:Macrophages / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D007455:Iodine; D002784:Cholesterol; D008071:Lipoprotein Lipase