Microvascular patterning is controlled by fine-tuning the Akt signal

Proc Natl Acad Sci U S A. 2005 Jan 4;102(1):128-33. doi: 10.1073/pnas.0403198102. Epub 2004 Dec 20.

Abstract

We investigated the functions of Akt during vascular development and remodeling by using an inducible endothelial cell-specific driver of the dominant-active myrAkt. We found that sustained signaling in response to overexpression of myrAkt led to embryonic lethality, edema, and vascular malformations. In addition to the morphological malformations, the vascular phenotype was consistent with a failure in remodeling, such that the normal patterning and vessel hierarchy was disturbed. Examination of the well studied retinal vasculature during the remodeling phases revealed that transient expression of myrAkt was capable of altering the normal response to oxygen-induced remodeling without causing vascular malformations. These findings suggest that physiological levels of Akt signaling modulated microvascular remodeling and support the hypothesis that, although Akt may be required for vascular growth and homeostasis, appropriate down-regulation is also an essential aspect of normal vascular patterning.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Physiologic / physiology*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • RNA, Messenger / metabolism
  • Retinal Vessels / abnormalities
  • Retinal Vessels / metabolism
  • Signal Transduction / physiology*
  • Skin / blood supply
  • Skin / embryology

Substances

  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt