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


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.


CONCLUSIONS
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.
Beijing Institute of Geriatrics, Beijing Hospital and Key Laboratory of Geriatrics, Ministry of Health, Beijing, China.
Xiyun
X
Liu
Gexin
G
Zhao
Yan
Y
Yan
Li
L
Bao
Beidong
B
Chen
Ruomei
R
Qi
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D050197:Atherosclerosis / Q000188:drug therapy / Q000235:genetics*; D001792:Blood Platelets / Q000187:drug effects; D023201:CD40 Ligand / Q000378:metabolism; D018946:Chemokine CCL5 / Q000097:blood / Q000378:metabolism; D046934:Ginkgolides / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000097:blood / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014657:Vasculitis / Q000188:drug therapy / Q000235:genetics*
D001057:Apolipoproteins E; D018946:Chemokine CCL5; D046934:Ginkgolides; D007783:Lactones; D008055:Lipids; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D023201:CD40 Ligand; D010978:Platelet Factor 4; C045856:ginkgolide B; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt