From vessel sprouting to normalization: role of the prolyl hydroxylase domain protein/hypoxia-inducible factor oxygen-sensing machinery.
The accepted model of vessel branching distinguishes several endothelial cell fates. At the forefront of a vessel sprout, "tip cells" guide the sprouting vessel toward an angiogenic stimulus. Behind the tip, "stalk cells" proliferate to elongate the vessel branch and create a lumen. In mature vessels, endothelial cells acquire a streamlined shape to optimally conduct blood flow. For this purpose, endothelial cells switch to the "phalanx" cell fate, which is characterized by quiescent and nonproliferating cells aligned in a tight cobblestonelike layer. Vessel maturation also requires the recruitment of mural cells (ie, smooth muscle cells and pericytes). These cell fates are often altered in pathological conditions, most prominently during the formation of tumor vasculature. Given the essential role of hypoxia as the driving force for initiating angiogenesis, it is not surprising that the hypoxia-sensing machinery controls key steps in physiological and pathological angiogenesis.
Vesalius Research Center, Vlaams Instituut voor Biotechnologie, Katholieke Universiteit Leuven, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
Cathy
C
Coulon
Maria
M
Georgiadou
Carmen
C
Roncal
Katrien
K
De Bock
Tobias
T
Langenberg
Peter
P
Carmeliet
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D016922:Cellular Senescence; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D010100:Oxygen / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000201:enzymology; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010100:Oxygen; D011393:Procollagen-Proline Dioxygenase; D000099162:Endothelial PAS Domain-Containing Protein 1