FOXOs in the maintenance of vascular homoeostasis.
The mammalian FoxO (forkhead box O) transcription factors FoxO1, FoxO3 and FoxO4 represent one of several effector arms of the PI3K (phosphoinositide 3-kinase)-Akt signalling network that has been linked to cancer, metabolism and aging. Specific roles of the FoxOs in the vascular cell types have been investigated to reveal that they play redundant yet critical roles in the proliferation and survival of ECs (endothelial cells). Somatic deletions of all FoxOs engendered progressive, widespread and highly penetrant haemangiomas associated with altered proliferative/survival dynamics of ECs in our genetic model. Related work by Akt-FoxO manipulation reported differentially regulated genes in ECs that may represent novel FoxO targets, controlling EC growth and morphogenesis and mediating many of the consequences of FoxO inactivation in the endothelium. Further studies on the action of these surrogate genes may provide important new insights into how the PI3K-Akt-FoxO pathway could be exploited clinically to treat vascular diseases and lead to the invention of novel therapeutic approaches. Here recent studies elucidating the role of FoxOs in the maintenance of vascular homoeostasis and supporting that the mammalian FoxO family serves essential roles in the maintenance of vascular stability and the suppression of aberrant vascular outgrowth are discussed.
Paik
J-H
JH
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. Jihye_Paik@dfci.harvard.edu
D000818:Animals; D001808:Blood Vessels / Q000502:physiology*; D002453:Cell Cycle; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D006706:Homeostasis; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D051858:Forkhead Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt