Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low-density lipoproteins.
Oxidized lipoproteins have been identified in atherosclerotic plaques and in early lesions in humans as well as in animals. There is accumulating evidence that such oxidized lipoproteins have an important role in atherosclerosis. Treatment of endothelial cells with altered lipoproteins stimulates monocyte binding as well as the production of chemotactic factors for monocytes. Both these findings could be relevant to the accumulation of monocytes-macrophages in the arterial wall during the early stages of lesion development. We now report that treatment of endothelial cells (EC) with modified low-density lipoproteins obtained by mild iron oxidation or by prolonged storage, results in a rapid and large induction of the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage CSF (M-CSF) and granulocyte CSF (G-CSF). These growth factors affect the differentiation, survival, proliferation, migration and metabolism of macrophages/granulocytes, and G-CSF and GM-CSF also affect the migration and proliferation of EC. Because EC and macrophages are important in the development of atherosclerosis, the expression of the CSFs by these cells could contribute to the disease.
Rajavashisth
T B
TB
Department of Medicine, UCLA 90024.
Andalibi
A
A
Territo
M C
MC
Berliner
J A
JA
Navab
M
M
Fogelman
A M
AM
Lusis
A J
AJ
D001011:Aorta; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000235:genetics*; D015342:DNA Probes; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005296:Ferrous Compounds / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000096:biosynthesis
D003115:Colony-Stimulating Factors; D015342:DNA Probes; D005296:Ferrous Compounds; D006133:Growth Substances; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor