Macrophage colony stimulating factor prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits.
The early atherosclerotic lesion is characterized by the presence of macrophage-derived foam cells. Macrophage colony stimulating factor (M-CSF) specifically stimulates the functions of the monocyte-macrophages. To elucidate the effects of M-CSF in the atherogenic process in vivo, we administered human recombinant M-CSF into Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for familial hypercholesterolemia. Three hundred micrograms of M-CSF were intravenously injected into WHHL rabbits aged 2.5 months, three times a week for 8.5 months. After the M-CSF treatment, we found very retarded progression of atherosclerosis. The accumulation of cholesterol ester was remarkably decreased in the aortae of M-CSF-treated animals (0.60 +/- 0.32 mg/g tissue), as compared to those of controls (4.32 +/- 0.61 mg/g tissue). Furthermore, the percentage of the surface area of the aorta with macroscopic plaque in animals treated with M-CSF was 14.3 +/- 6.2%, much less than that in controls receiving saline injection (38.8 +/- 8.0%). Thus, M-CSF definitely prevented the progression of atherosclerosis in WHHL rabbits by influencing macrophage functions.
Inoue
I
I
3rd Department of Internal Medicine, University of Tokyo, Japan.
Inaba
T
T
Motoyoshi
K
K
Harada
K
K
Shimano
H
H
Kawamura
M
M
Gotoda
T
T
Oka
T
T
Shiomi
M
M
Watanabe
Y
Y
D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D002788:Cholesterol Esters / Q000032:analysis; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000473:pathology*; D008055:Lipids / Q000097:blood; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000502:physiology*; D011817:Rabbits; D011994:Recombinant Proteins
D002788:Cholesterol Esters; D008055:Lipids; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor