title: Calmodulin is essential for angiogenesis in response to hypoxic stress in endothelial cells.
abstract: Angiogenesis, the formation of new blood vessels that is regulated by hypoxia, is a critical process for the growth and spread of tumors. Multiple phases of this process, including migration, adhesion, and formation of new capillary tubes, are needed for optimal tumor growth. Here, a new regulatory function for Ca2+-CaM in the vascular endothelium is described. Ca2+-CaM activation induced by hypoxia in endothelial cells is essential for angiogenic cellular responses. Inhibition of Ca2+-CaM activity suppressed endothelial cell migration, adhesion on collagen I substrate, invasion and impaired in vitro endothelial cell differentiation into tube-like structures. We also reported that CaM is co-distributed with the actin structures in the lamellipodia in migrating cells, whereas the actin cytoskeleton rearrangement induced by hypoxia was disrupted and HIF-1 transcriptional activity was decreased when treated with CaM antagonists into cultures. These data indicate that Ca2+-CaM activation is more closely associated with the regulation of angiogenic key events, especially in response to hypoxic stress.
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Nanjing Normal University, Nanjing, P R China.
authors.forename: Wei-Gan
authors.initials: WG
authors.lastname: Shen
authors.forename: Wan-Xin
authors.initials: WX
authors.lastname: Peng
authors.forename: Gu
authors.initials: G
authors.lastname: Dai
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Xu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chao-Jun
authors.initials: CJ
authors.lastname: Li
mesh_terms: D000199:Actins / Q000378:metabolism; D020013:Calcium Signaling; D002147:Calmodulin / Q000378:metabolism*; D002448:Cell Adhesion; D015687:Cell Hypoxia; D002465:Cell Movement; D024042:Collagen Type I / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic; D021381:Protein Transport; D011554:Pseudopodia / Q000378:metabolism
chemical_list: D000199:Actins; D002147:Calmodulin; D024042:Collagen Type I; D051793:Hypoxia-Inducible Factor 1