Anti-atherosclerotic effect of cilostazol in apolipoprotein-E knockout mice.
To investigate whether cilostazol (CAS 73963-72-1), a selective phosphodiesterase 3 inhibitor, reduces the progression of atherogenic diet-induced atherosclerosis, cilostazol was orally administered twice a day for 4 weeks to male apolipoprotein-E knockout (ApoE KO) mice. In serial sections of the aortic root, the atherosclerotic lesion ratios in the cilostazol-treated groups (32.5 +/- 3.3% for 100 mg/kg, 29.0 +/- 2.9% for 300 mg/kg) were significantly and dose-dependently smaller than that of the control group (40.2 +/- 3.7%). Cilostazol also significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte/macrophage accumulation in the aortic root and increased high-density lipoprotein(HDL) cholesterol levels in plasma. These results suggest that cilostazol suppresses the progression of atherosclerosis in ApoE KO mice by inhibiting adhesionand infiltration of monocytes and reducing cholesterol accumulation in atherosclerotic lesion.
Takase
Hiromichi
H
Circulation I Research Group, Research Institute of Pharmacological & Therapeutical Development, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan. h_takase@research.otsuka.co.jp
Hashimoto
Ayako
A
Okutsu
Reiko
R
Hirose
Yoshimi
Y
Ito
Hideki
H
Imaizumi
Takashi
T
Miyakoda
Goro
G
Mori
Toyoki
T
D000375:Aging / Q000502:physiology; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D000077407:Cilostazol; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000097:blood / Q000627:therapeutic use*; D013777:Tetrazoles / Q000097:blood / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008055:Lipids; D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D014280:Triglycerides; D019010:Vascular Cell Adhesion Molecule-1; D002784:Cholesterol; D000077407:Cilostazol