Ginkgolide B reduces atherogenesis and vascular inflammation in ApoE(-/-) mice.

Abstract

AIMS:

To investigate whether ginkgolide B (a platelet-activating factor inhibitor) affects vascular inflammation in atherosclerosis-prone apolipoprotein E-deficient (ApoE(-/-)) mice.

METHODS AND RESULTS:

Human platelets were used to evaluate the effects of ginkgolide B on platelet aggregation and signal transduction. Ginkgolide B attenuated platelet aggregation and inhibited phosphatidylinositol 3 kinase (PI3K) activation and Akt phosphorylation in thrombin- and collagen-activated platelets. ApoE(-/-) mice were administered a high-cholesterol diet for 8 weeks. Plasma platelet factor 4 (PF4) and RANTES (regulated upon activation, normal T-cell expressed, and secreted protein) were then measured using an enzyme-linked immunosorbent assay. Scanning electron microscopy and immunohistochemistry were used to determine atherosclerotic lesions. Ginkgolide B decreased plasma PF4 and RANTES levels in ApoE(-/-) mice. Scanning electron microscopic examination showed that ginkgolide B reduced aortic plaque in ApoE(-/-) mice. Immunohistochemistry analysis demonstrated that ginkgolide B diminished P-selectin, PF4, RANTES, and CD40L expression in aortic plaque in ApoE(-/-) mice. Moreover, ginkgolide B suppressed macrophage and vascular cell adhesion protein 1 (VCAM-1) expression in aorta lesions in ApoE(-/-) mice. Similar effects were observed in aspirin-treated ApoE(-/-) mice.

CONCLUSION:

Ginkgolide B significantly reduced atherosclerotic lesions and P-selectin, PF4, RANTES, and CD40L expression in aortic plaque in ApoE-/- mice. The efficacy of ginkgolide B was similar to aspirin. These results provide direct evidence that ginkgolide B inhibits atherosclerosis, which may be associated with inhibition of the PI3K/Akt pathway in activated platelets.

• Authors: Xiyun Liu, Gexin Zhao, Yan Yan, Li Bao, Beidong Chen, Ruomei Qi
• Journal: PloS one (PLoS One) Vol. 7 Issue 5 Pg. e36237 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22662117 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Chemokine CCL5
• Ginkgolides
• Lactones
• Lipids
• P-Selectin
• Vascular Cell Adhesion Molecule-1
• CD40 Ligand
• Platelet Factor 4
• ginkgolide B
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Aorta (drug effects, metabolism, pathology)
• Apolipoproteins E (deficiency, genetics)
• Atherosclerosis (drug therapy, genetics)
• Blood Platelets (drug effects)
• CD40 Ligand (metabolism)
• Chemokine CCL5 (blood, metabolism)
• Ginkgolides (administration & dosage, pharmacology)
• Humans
• Lactones (administration & dosage, pharmacology)
• Lipids (blood)
• Macrophages (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• P-Selectin (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation (drug effects)
• Plaque, Atherosclerotic (metabolism)
• Platelet Activation
• Platelet Aggregation (drug effects)
• Platelet Factor 4 (blood, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Vascular Cell Adhesion Molecule-1 (metabolism)
• Vasculitis (drug therapy, genetics)