| First Author | Rajavashisth T | Year | 1998 |
| Journal | J Clin Invest | Volume | 101 |
| Issue | 12 | Pages | 2702-10 |
| PubMed ID | 9637704 | Mgi Jnum | J:48300 |
| Mgi Id | MGI:1267150 | Doi | 10.1172/JCI119891 |
| Citation | Rajavashisth T, et al. (1998) Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor- deficient mice. J Clin Invest 101(12):2702-10 |
| abstractText | Previous studies of osteopetrotic (op) mice lacking macrophage colony-stimulating factor (M-CSF) have revealed an inhibition of atherosclerosis development in the apolipoprotein E (apo E)-deficient model and in a diet- induced model. Using LDH, receptor-deficient mice, we now show that atheroma development depends on M-CSF concentration, as not only did homozygous osteopetrotic (op/op) mice have dramatically reduced lesions (similar to 0.3% of control lesion size) but heterozygous (op/+) mice had lesions <1% of controls. Mice heterozygous for the op mutation (op/+) had plasma levels of M-CSF about half those in controls (+/+), The finding that an similar to 2- fold reduction in M-CSF expression reduced lesion size similar to 100-fold suggests the requirement for a threshold level of M-CSF. The effect of M-CSF on atherosclerosis did not appear to be mediated either by changes in plasma lipoprotein levels or alterations in the number of circulating monocytes, since both op/op and op/+ mice exhibited higher levels of atherogenic lipoprotein particles and (op/+) mice showed a near normal number of circulating monocytes, EDL receptor-null littermates of genotypes from op/op, op/+, to +/+ showed monocyte differentials of similar to 4.5, 8, and 10%, respectively. Taken together, these results suggest that the effects of M-CSF on atherogenesis may not be mediated by expression of M-CSF systemically or by modulation of the number of circulating monocytes. These studies support the conclusion that M-CSF participates critically in fatty streak formation and progression to a complex fibrous lesion. |
