on March 27, 2003
Published online before print March 27, 2003, doi: 10.1161/01.ATV.0000069208.20268.D0
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Submitted on January 17, 2003
Accepted on March 14, 2003
Lysophosphatidylcholine Regulates Synthesis of Biglycan and the Proteoglycan Form of Macrophage Colony Stimulating Factor
Mary Y. Chang *;
From the Department of Medicine, University of Washington (M.Y.C., A.C.), and the Hope Heart Institute (C.T., T.N.W.), Seattle, Wash.
* To whom correspondence should be addressed. E-mail: mychang{at}u.washington.edu.
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.
Methods and Results--Those tested included 2 oxysterols (7-ketocholesterol and 7
-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.
Key words: lysophosphatidylcholine • oxidized LDL • proteoglycan • biglycan • proteoglycan form of macrophage colony stimulating factor
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