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Updated: Jul 14, 2026
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Anti-atherosclerotic effect of cilostazol in apolipoprotein-E knockout mice
Hiromichi Takase1, Ayako Hashimoto, Reiko Okutsu
1Circulation I Research Group, Research Institute of Pharmacological & Therapeutical Development, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan. h_takase@research.otsuka.co.jp
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 adhesionand infiltration of monocytes and reducing cholesterol accumulation in atherosclerotic lesion.
Insights
Cilostazol, a phosphodiesterase 3 inhibitor, significantly reduced atherosclerosis progression in mice. This drug also decreased inflammatory markers and improved cholesterol levels, suggesting a therapeutic benefit.
Area of Science:
- Pharmacology
- Cardiovascular Research
- Atherosclerosis Studies
Background:
- Atherosclerosis is a major cause of cardiovascular disease.
- Apolipoprotein-E knockout (ApoE KO) mice are a standard model for studying atherosclerosis.
- Selective phosphodiesterase 3 (PDE3) inhibitors are being investigated for cardiovascular benefits.
Purpose of the Study:
- To evaluate the efficacy of cilostazol in reducing the progression of diet-induced atherosclerosis in ApoE KO mice.
- To investigate the mechanisms underlying cilostazol's potential anti-atherosclerotic effects.
Main Methods:
- Male ApoE KO mice were fed an atherogenic diet and treated with cilostazol (100 or 300 mg/kg) or vehicle for 4 weeks.
- Atherosclerotic lesion size in the aortic root was quantified.
- Expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte/macrophage accumulation were assessed.
- Plasma high-density lipoprotein (HDL) cholesterol levels were measured.
Main Results:
- Cilostazol significantly and dose-dependently reduced atherosclerotic lesion ratios in the aortic root compared to controls.
- Treatment with cilostazol led to a significant reduction in VCAM-1 expression and monocyte/macrophage accumulation.
- Cilostazol administration resulted in increased plasma HDL cholesterol levels.
Conclusions:
- Cilostazol effectively suppresses the progression of atherosclerosis in ApoE KO mice.
- The anti-atherosclerotic effects of cilostazol may be mediated by inhibiting monocyte adhesion and infiltration.
- Cilostazol's ability to improve lipid profiles and reduce inflammation contributes to its atheroprotective properties.
