Role of macrophage colony-stimulating factor in atherosclerosis: studies of osteopetrotic mice.
- 1 May 1997
- journal article
- Vol. 150 (5), 1687-99
Abstract
Previous in vitro and in vivo studies have suggested that macrophage colony-stimulating factor (M-CSF) plays a role in atherogenesis. To examine this hypothesis, we have studied atherogenesis in osteopetrotic (op/op) mice, which lack M-CSF due to a structural gene mutation. Atherogenesis was induced either by feeding the mice a high fat, high cholesterol diet or by crossing op mice with apolipoprotein E (apo E) knockout mice to generate mice lacking both M-CSF and apo E. In both the dietary and apo E knockout models, M-CSF deficiency resulted in significantly reduced atherogenesis. For example, in the apo E knockout model, homozygosity for the op mutation totally abolished aortic atherogenesis in male mice and reduced the size of the lesions approximately 97% in female mice. Mice heterozygous for the op mutation also exhibited a significant decrease in lesion size. Among apo E knockout mice, the frequency of atherosclerosis in aortic arch was 0/6 (op/op), 1/15 (op/+), and 12/16 (+/+). The effect of the M-CSF on atherosclerosis did not appear to be mediated by changes in plasma lipoproteins, as the op mice exhibited higher levels of atherogenic lipoprotein particles. The effects of the op mutation on atherogenesis may have resulted from decreased circulating monocytes, reduced tissue macrophages, or diminished arterial M-CSF.This publication has 42 references indexed in Scilit:
- Genetic Determination of Cartilaginous Metaplasia in Mouse AortaArteriosclerosis, Thrombosis, and Vascular Biology, 1995
- Transcriptional Activation of the Macrophage-Colony Stimulating Factor Gene by Minimally Modified LDLArteriosclerosis, Thrombosis, and Vascular Biology, 1995
- Recombinant human macrophage colony-stimulating factor reduces plasma cholesterol and carrageenan granuloma foam cell formation in Watanabe heritable hyperlipidemic rabbits.Arteriosclerosis and Thrombosis: A Journal of Vascular Biology, 1994
- Immune-complex-mediated vasculitis increases coronary artery lipid accumulation in autoimmune-prone MRL mice.Arteriosclerosis and Thrombosis: A Journal of Vascular Biology, 1993
- The pathogenesis of atherosclerosis: a perspective for the 1990sNature, 1993
- Spontaneous Hypercholesterolemia and Arterial Lesions in Mice Lacking Apolipoprotein EScience, 1992
- Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells.Proceedings of the National Academy of Sciences of the United States of America, 1992
- Effects of human recombinant macrophage colony-stimulating factor on the secretion of lipoprotein lipase from macrophages.Arteriosclerosis and Thrombosis: A Journal of Vascular Biology, 1991
- SERUM CHOLESTEROL-LOWERING ACTIVITY OF HUMAN MONOCYTIC COLONY-STIMULATING FACTORThe Lancet, 1989
- The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF 1Cell, 1985