Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low-density lipoproteins

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Abstract
OXIDIZED lipoproteins have been identified in atherosclerotic plaques1,2 and in early lesions3,4 in humans as well as in animals. There is accumulating evidence that such oxidized lipoproteins have an important role in atherosclerosis5–7. Treatment of endothelial cells with altered lipoproteins stimulates monocyte binding8 as well as the production of chemotactic factors for monocytes9. 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/granulocytes10,11, and G–CSF and GM–CSF also affect the migration and proliferation of EC12. Because EC and macrophages are important in the development of atherosclerosis, the expression of the CSFs by these cells could contribute to the disease.