FOXOs in the maintenance of vascular homoeostasis.

TitleFOXOs in the maintenance of vascular homoeostasis.
Publication TypeJournal Article
Year of Publication2006
AuthorsPaik J-H
JournalBiochem Soc Trans
Volume34
IssuePt 5
Pagination731-4
Date Published2006 Nov
ISSN0300-5127
KeywordsAnimals, Blood Vessels, Cell Cycle, Forkhead Transcription Factors, Gene Deletion, Homeostasis, Humans, Muscle, Smooth, Vascular, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt
Abstract

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.

DOI10.1042/BST0340731
Alternate JournalBiochem Soc Trans
PubMed ID17052184
Related Faculty: 
Ji-Hye Paik, Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700