title: Acetylbritannilactone Modulates Vascular Endothelial Growth Factor Signaling and Regulates Angiogenesis in Endothelial Cells.
abstract: The present study was conducted to determine the effects of 1-O-acetylbritannilactone (ABL), a compound extracted from Inula britannica L., on vascular endothelial growth factor (VEGF) signaling and angiogenesis in endothelial cells (ECs). We showed that ABL promotes VEGF-induced cell proliferation, growth, migration, and tube formation in cultured human ECs. Furthermore, the modulatory effect of ABL on VEGF-induced Akt, MAPK p42/44, and p38 phosphorylation, as well as on upstream VEGFR-2 phosphorylation, were associated with VEGF-dependent Matrigel angiogenesis in vivo. In addition, animals treated with ABL (26 mg/kg/day) recovered blood flow significantly earlier than control animals, suggesting that ABL affects ischemia-mediated angiogenesis and arteriogenesis in vivo. Finally, we demonstrated that ABL strongly reduced the levels of VEGFR-2 on the cell surface, enhanced VEGFR-2 endocytosis, which consistent with inhibited VE-cadherin, a negative regulator of VEGF signaling associated with VEGFR-2 complex formation, but did not alter VE-cadherin or VEGFR-2 expression in ECs. Our results suggest that ABL may serve as a novel therapeutic intervention for various cardiovascular diseases, including chronic ischemia, by regulating VEGF signaling and modulating angiogenesis.
authors: Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China.
authors: Jingshan
authors: J
authors: Zhao
authors: Department of Nephrology, Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China.|Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, 050071, China.
authors: Honglin
authors: H
authors: Niu
authors: Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China.
authors: Aiying
authors: A
authors: Li
authors: Key Laboratory of Medical Biotechnology of Hebei Province and Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, China.|Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, 050017, China.
authors: Lei
authors: L
authors: Nie
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D006614:Hindlimb / Q000098:blood supply; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007511:Ischemia / Q000503:physiopathology; D007783:Lactones / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D043925:Angiogenesis Inducing Agents; D015703:Antigens, CD; D015820:Cadherins; D007783:Lactones; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099152:Cadherin 5; C467484:VEGFA protein, human; C487680:acetylbritannilatone