title: Effects of recombinant human macrophage colony-stimulating factor on atherosclerotic lesions established in the aorta of high cholesterol-fed rabbits.
abstract: Anti-atherosclerotic effects of human macrophage colony-stimulating factor were investigated using rabbits fed a high cholesterol diet. Rabbits fed a diet containing 2% cholesterol for 59 days developed hyperlipidemia and atheromatous aortic plaques. They were then administered 80 microg/kg/day of either macrophage colony-stimulating factor or human serum albumin, as a control, for the next 12 weeks. Compared with the control group, rabbits treated with macrophage colony-stimulating factor had significantly fewer plaques on the inner surface of the thoracic and abdominal aortae, and half the sectional area of thickened intima in the aortic arch, as well as in the thoracic and abdominal aortae. Macrophage colony-stimulating factor also decreased the cholesterol content of the atherosclerotic lesions. Serobiochemical analyses revealed that macrophage colony-stimulating factor increased the levels of high density lipoprotein-cholesterol significantly, without influencing other lipid parameters such as the level of low density lipoproteins. The effects of macrophage colony-stimulating factor were evident until the fourth week of drug injection, at which time anti-human macrophage colony-stimulating factor antibodies were clearly induced in the serum. These results indicate that exogenously administered macrophage colony-stimulating factor suppresses atherosclerotic lesions induced by a high cholesterol diet by activating lipid metabolism in vivo.
authors.affiliation: Pharmaceutical Research Division, Welfide Corporation, Shodai-Ohtani, Hirakata, Osaka 573-1153, Japan. ac45560@welfide.co.jp
authors.forename: H
authors.initials: H
authors.lastname: Irie
authors.forename: H
authors.initials: H
authors.lastname: Koshiba
authors.forename: M
authors.initials: M
authors.lastname: Koyama
authors.forename: E
authors.initials: E
authors.lastname: Asakura
authors.forename: H
authors.initials: H
authors.lastname: Shibata
authors.forename: K
authors.initials: K
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Naito
authors.forename: T
authors.initials: T
authors.lastname: Yamauchi
authors.forename: K
authors.initials: K
authors.lastname: Yada
authors.forename: T
authors.initials: T
authors.lastname: Hanamura
authors.forename: S
authors.initials: S
authors.lastname: Hanada
authors.lastname: Abe Si
authors.forename: N
authors.initials: N
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D002784:Cholesterol / Q000032:analysis; D002914:Chylomicrons / Q000097:blood / Q000187:drug effects*; D004195:Disease Models, Animal; D008075:Lipoproteins, HDL / Q000097:blood / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000097:blood / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D012709:Serum Albumin / Q000494:pharmacology; D017539:Tunica Intima / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D002914:Chylomicrons; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011994:Recombinant Proteins; D012709:Serum Albumin; D016173:Macrophage Colony-Stimulating Factor; D002784:Cholesterol