Regulation of cell growth by oxidized LDL.
The first reports of the influences of oxidized LDL (oxLDL) on cell function pertained to negative effects on cell growth-growth arrest, injury, and toxicity. Since these studies, it has become apparent that sublethal levels of oxLDL cause some, but not all, cells to proliferate. This review highlights the growth-promoting effects of oxLDL rather than its inhibitory or injurious effects. Smooth muscle cells (SMCs) and monocyte-macrophages proliferate after exposure to oxLDL; endothelial cells do not. Scavenger receptors are involved in the proliferative effects on monocyte-macrophages, whereas the effects of oxLDL on SMCs appear to be receptor independent. Lysophosphatidylcholine (lysoPC), and structurally related lipids are among the growth-promoting constituents of oxLDL. OxLDL exerts at least a part of its effects by inducing expression or causing the release of growth factors. OxLDL (or lysoPC) can cause the release of basic fibroblast growth factor (bFGF) from SMCs; oxLDL (or lysoPC) can induce heparin binding EGF-like growth factor (HB-EGF) synthesis and release from macrophages. An imposing array of changes in cytokine and growth factor expression and/or release can be imposed by oxLDL on a wide variety of cell types. These effects and the studies probing the cell signaling events leading to them are described.
Chisolm
G M
GM
Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. chisolg@ccf.org
Chai
Y
Y
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D016207:Cytokines; D006133:Growth Substances; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; C099252:oxidized low density lipoprotein