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Wenyang Huoxue Jiedu formula inhibits thin-cap fibroatheroma plaque formation via the VEGF/VEGFR signaling pathway

Chen, Shuang, Ye, Zi-Qing, Li, Zhi-Wen, Zhao, Chun-Xiao, Chen, Guang-Jin, Zhou, Jun-Zhuo, Wang, Chuan, Huang, Rui-Li, Hong, Yong-Dun
Journal of ethnopharmacology 2018 v.219 pp. 213-221
Oriental traditional medicine, blood serum, capillary electrophoresis, coronary disease, gene expression, human umbilical vein endothelial cells, immunoassays, immunohistochemistry, in vivo studies, messenger RNA, mice, models, quantitative polymerase chain reaction, rats, signal transduction, staining, vascular endothelial growth factor receptor-2, vascular endothelial growth factors
For many years, Guangzhou University of Chinese Medicine has been successfully using the empirical Wenyang Huoxue Jiedu formula (WHJF) to treat coronary heart disease. Modern theories of acute coronary syndrome mainly focus on rupture of thin-cap fibroatheromas (TCFAs), which is closely related to the release of vascular endothelial growth factor and its receptor (VEGF/VEGFR).We investigated the effects of WHJF on the formation of TCFA plaques and the potential mechanism (VEGF/VEGFR signaling pathway).For the in vivo experiments, WHJF was administered to ApoE-/- mice, as a model of TCFA plaque formation. Aortic sections of the mice were obtained, and the vulnerability index and new vessel density of plaques were calculated by the Movat staining assay and immunohistochemistry kit, respectively. Protein and mRNA expression levels of VEGF/VEGFR in aortas were assayed by capillary electrophoresis immunoassay and quantitative real-time polymerase chain reaction analyses. In vitro, WHJF serum was produced in rats on the fourth day 2 h after the first administration of different concentrations of WHJF. Proliferation, migration, and lumen formation ability of human umbilical vein endothelial cells (HUVECs) treated with sera from these rats were assayed by the CKK-8 kit, Transwell plates, and Matrigel assay, respectively. Protein and mRNA expression levels of signaling molecules in the VEGF/VEGFR pathways were also examined.In vivo, the vulnerability index and new vessel density of plaques in the WHJF group were lower than those values in the blank control group (P < 0.05). No differences were found between the groups in the expression levels of VEGF/VEGFR (P > 0.05). In vitro, the proliferation, migration, and tube formation of HUVECs in the high-dose WHJF group were reduced compared to the control group (P < 0.05). This finding was in agreement with the downregulation of VEGFR-2 and pERK (P < 0.05). The mRNA expression of signaling molecules showed no difference between the groups (P > 0.05).WHJF inhibits TCFA formation by influencing the VEGF/VEGFR signaling pathway.