Plasma cholesterol-lowering activity of monocyte colony-stimulating factor (M-CSF).
We investigated the action of monocyte colony-stimulating factor (M-CSF) on plasma cholesterol metabolism. Recombinant human monocyte colony-stimulating factor (rhM-CSF) was intravenously injected into Watanabe heritable hyperlipidemic (WHHL) rabbits that were deficient in LDL receptor. The treated rabbits showed decreases in plasma total cholesterol levels from 493 +/- 39 to 416 +/- 45 mg/dl (about 15%) during the treatment. The decrease in total plasma cholesterol level was due to decreased levels of lipoproteins containing apo B 100 such as VLDL, IDL, and LDL. The effect of M-CSF on the LDL-receptor-deficient animal in vivo and evidence from Northern blot analysis of liver suggested that M-CSF lowers plasma cholesterol level through activated uptake of lipoproteins containing apo B 100 via pathways other than the hepatic LDL receptor. We have started a clinical study to evaluate the plasma cholesterol-lowering effect of M-CSF in patients with familial hypercholesterolemia, and have observed a decreased in total plasma cholesterol level in one of three patients treated with M-CSF. M-CSF may provide new insight into plasma cholesterol metabolism and a possible new tool to treat patients with hypercholesterolemia and atherosclerosis.
Shimano
H
H
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Yamada
N
N
Motoyoshi
K
K
Matsumoto
A
A
Ishibashi
S
S
Mori
N
N
Takaku
F
F
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000378:metabolism; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D016173:Macrophage Colony-Stimulating Factor; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011973:Receptors, LDL / Q000378:metabolism; D011994:Recombinant Proteins
D008078:Cholesterol, LDL; D003115:Colony-Stimulating Factors; D012333:RNA, Messenger; D011973:Receptors, LDL; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D002784:Cholesterol