Dexamethasone-induced suppression of aortic atherosclerosis in cholesterol-fed rabbits. Possible mechanisms.
We investigated the mechanisms by which corticosteroids affect atherosclerosis. Male New Zealand White rabbits were injected with 0.125 mg dexamethasone (n = 10) or vehicle (control group, n = 10). Both groups were fed a 1% cholesterol diet for 8 weeks. Although the dexamethasone-treated animals exhibited a greater degree of hyperlipidemia, they exhibited significantly less atherosclerotic plaque of the aortic surface than control animals (7.8% versus 47.2%). Immunofluorescence study of the aortic plaque specimens showed that dexamethasone administration reduced both macrophages and T lymphocytes. In vitro, dexamethasone suppressed the proliferation and differentiation of U937 cells and inhibited uptake and degradation of beta-very low density lipoproteins by mouse peritoneal macrophages. These findings suggest that dexamethasone suppresses the development of atherosclerosis in the aorta of rabbits by inhibiting recruitment and proliferation of macrophages and the formation of foam cells in plaques.
Asai
K
K
Department of Geriatrics, Nagoya University School of Medicine, Japan.
Funaki
C
C
Hayashi
T
T
Yamada
K
K
Naito
M
M
Kuzuya
M
M
Yoshida
F
F
Yoshimine
N
N
Kuzuya
F
F
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001161:Arteriosclerosis / Q000276:immunology / Q000517:prevention & control*; D001835:Body Weight; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003907:Dexamethasone / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D015473:Leukemia, Promyelocytic, Acute; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D009929:Organ Size; D010529:Peritoneal Cavity / Q000166:cytology; D011817:Rabbits; D013601:T-Lymphocytes / Q000166:cytology; D014407:Tumor Cells, Cultured / Q000166:cytology
D002791:Cholesterol, Dietary; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D003907:Dexamethasone