title: The effects of cadmium on VEGF-mediated angiogenesis in HUVECs.
abstract: Cadmium (Cd) is a highly toxic element that causes morphologic alterations and dysfunction in blood vessels. The altered vascular function caused by cadmium has been implicated in a range of chronic diseases, including hypertension. The effects of cadmium are a multisystem phenomenon involving inflammation, hypertrophy, apoptosis, angiogenesis and important processes involved in vascular remodeling systems. Vascular endothelial growth factor (VEGF) plays a major role in cell growth and angiogenesis under pathologic conditions. VEGF secretion is related to anti-apoptosis protein expression and attenuates apoptosis in endothelial cells. This study examined the VEGF-dependent mechanisms of angiogenesis and apoptosis in cadmium-treated endothelial cells (HUVECs). The effects and mechanisms of cadmium in endothelial cells (HUVECs) were examined by exposing the cells to different doses of cadmium chloride (2.5-40 μ m). After the cadmium treatment, the angiogenesis and apoptosis mechanisms related to VEGF in cadmium-treated HUVECs were examined. As a result, the low concentration of cadmium increased the tube formation in HUVECs. In addition, cadmium at concentrations of 5 and 10 μ m increased VEGF secretion and VEGFR2 activity, which suggest that cadmium affects the growth of blood vessels. All three MAPK pathways, namely ERK, JNK and p38, were activated by cadmium in HUVECs. However, high concentrations of cadmium caused cell damage, disrupted tube formation and inhibited VEGF expression and the activities of VEGFR2 and MAPK in HUVECs. Cadmium has dual functions through VEGF-dependent mechanisms in a dose-dependent manner. In this study, the dual effects of cadmium might alter angiogenesis and induce apoptosis through VEGF pathways in HUVECs.
authors.affiliation: Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea.
authors.forename: Jisun
authors.initials: J
authors.lastname: Kim
authors.forename: Wonbong
authors.initials: W
authors.lastname: Lim
authors.forename: Youngjong
authors.initials: Y
authors.lastname: Ko
authors.forename: Hyukil
authors.initials: H
authors.lastname: Kwon
authors.forename: Sangwoo
authors.initials: S
authors.lastname: Kim
authors.forename: Oksu
authors.initials: O
authors.lastname: Kim
authors.forename: Gyeongju
authors.initials: G
authors.lastname: Park
authors.forename: Hongran
authors.initials: H
authors.lastname: Choi
authors.forename: Okjoon
authors.initials: O
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D002104:Cadmium; D040301:Vascular Endothelial Growth Factor Receptor-2; D020928:Mitogen-Activated Protein Kinases