Lysophosphatidylcholine regulates synthesis of biglycan and the proteoglycan form of macrophage colony stimulating factor.
OBJECTIVE
We have shown that copper-oxidized LDL (Ox-LDL) regulates proteoglycan synthesis by arterial smooth muscle cells. Ox-LDL specifically upregulates biglycan expression while causing elongation of glycosaminoglycan chains on all of the major secreted proteoglycans (biglycan, decorin, and versican), resulting in enhanced lipoprotein-binding interactions. It is not known which component of Ox-LDL is responsible for these effects. This study investigated the ability of several bioactive components of Ox-LDL to regulate proteoglycan synthesis.


RESULTS
Those tested included 2 oxysterols (7-ketocholesterol and 7beta-hydroxycholesterol) and 2 lysolipids (lysophosphatidylcholine and lysophosphatidic acid) formed during LDL oxidation. 7-ketocholesterol, lysophosphatidylcholine, and lysophosphatidic acid all increased proteoglycan MWapp, which is correlated with chain elongation and enhanced lipoprotein-binding properties in vitro. Lysophosphatidylcholine mimics the ability of Ox-LDL to stimulate biglycan expression and also causes a marked induction of the core protein for the proteoglycan form of macrophage colony stimulating factor.


CONCLUSIONS
Multiple oxidized lipid molecules can modulate proteoglycan synthesis and may have important consequences to atherogenesis via processes that involve enhanced lipoprotein retention as well as the promotion of macrophage survival and differentiation.
Chang
Mary Y
MY
Department of Medicine, University of Washington, Seattle, Wash 98195-6426, USA. mychang@u.washington.edu
Tsoi
Christina
C
Wight
Thomas N
TN
Chait
Alan
A
D000818:Animals; D058578:Biglycan; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005786:Gene Expression Regulation / Q000187:drug effects*; D006888:Hydroxycholesterols / Q000494:pharmacology; D007653:Ketocholesterols / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008246:Lysophospholipids / Q000494:pharmacology; D008254:Macaca nemestrina; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics
D058578:Biglycan; D016326:Extracellular Matrix Proteins; D006888:Hydroxycholesterols; D007653:Ketocholesterols; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D020033:Protein Isoforms; D011509:Proteoglycans; C099252:oxidized low density lipoprotein; C011724:cholest-5-en-3 beta,7 alpha-diol; D016173:Macrophage Colony-Stimulating Factor; C003001:7-ketocholesterol