Abstract
Abdominal aortic aneurysms (AAAs) are a chronic vascular disease characterized by pathological luminal dilation. Aortic rupture is the fatal consequence of AAAs. Ginkgo biloba extracts (GBEs), a natural herb extract widely used as food supplements, drugs, and cosmetics, has been reported to suppress development of calcium chloride-induced AAAs in mice. Calcium chloride-induced AAAs do not rupture, while angiotensin II (AngII)-induced AAAs in mice have high rate of aortic rupture, implicating potentially different mechanisms from calcium chloride-induced AAAs. This study aimed to determine whether GBE would improve aortic dilation and rupture rate of AngII-induced AAAs. Male apolipoprotein E (apoE) −/− mice were infused with AngII and administered either GBE or its major active ingredients, flavonoids and ginkgolides, individually or in combination. To determine the effects of GBE in mice with established AAAs, male apoE−/− mice were firstly infused with AngII for 28 days to develop AAAs, and then administered either GBE or vehicle in mice with established AAAs, which were continuously infused with AngII for another 56 days. GBE, but not the two major active components separately or synergistically, prevented aortic rupture, but not aortic dilation. The protection of GBE from aortic rupture was independent of systolic blood pressure, lipid, and inflammation. GBE also did not attenuate either aortic rupture or progressive aortic dilation in mice with established AAAs. GBE did not reduce the atherosclerotic lesion areas, either. In conclusion, GBE prevents aortic rupture in AngII-infused hypercholesterolemic mice, but only in the early phase of the disease development.
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Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (31371475, 31171392, and 81571932). We thank Dr. Jiyong Jing in the Department of Respiratory Therapy, Second Affiliated Hospital, Zhejiang University School of Medicine for helping statistical analyses.
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X.-j.X. conceived and designed the experiments; X.-f.H., S.-z.Z. and N.Z. performed the experiments; X.-j.X., H.L. and A.D. contributed new reagents or analytic tools; X.-f.H., X.-j.X. and Y.-y.Y. analyzed the data; X.-j.X., H.L. and A.D. wrote the manuscript.
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Huang, Xf., Zhang, Sz., You, Yy. et al. Ginkgo biloba extracts prevent aortic rupture in angiotensin II-infused hypercholesterolemic mice. Acta Pharmacol Sin 40, 192–198 (2019). https://doi.org/10.1038/s41401-018-0017-7
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DOI: https://doi.org/10.1038/s41401-018-0017-7
