Arzneimittelforschung 2007; 57(4): 185-191
DOI: 10.1055/s-0031-1296604
Cardiac Drugs · Cardiac Stimulants · Coronary Drugs
Editio Cantor Verlag Aulendorf (Germany)

Anti-atherosclerotic Effect of Cilostazol in Apolipoprotein-E Knockout Mice

Hiromichi Takase
1  Circulation I Research Group, Research Institute of Pharmacological & Therapeutical Development, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan
,
Ayako Hashimoto
1  Circulation I Research Group, Research Institute of Pharmacological & Therapeutical Development, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan
,
Reiko Okutsu
1  Circulation I Research Group, Research Institute of Pharmacological & Therapeutical Development, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan
,
Yoshimi Hirose
1  Circulation I Research Group, Research Institute of Pharmacological & Therapeutical Development, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan
,
Hideki Ito
1  Circulation I Research Group, Research Institute of Pharmacological & Therapeutical Development, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan
,
Takashi Imaizumi
1  Circulation I Research Group, Research Institute of Pharmacological & Therapeutical Development, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan
,
Goro Miyakoda
1  Circulation I Research Group, Research Institute of Pharmacological & Therapeutical Development, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan
,
Toyoki Mori
1  Circulation I Research Group, Research Institute of Pharmacological & Therapeutical Development, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan
› Author Affiliations
Further Information

Publication History

Publication Date:
21 December 2011 (online)

Abstract

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 adhesion and infiltration of monocytes and reducing cholesterol accumulation in atherosclerotic lesion.