Akt1/protein kinase B is critical for ischemic and VEGF-mediated angiogenesis (J. Clin. Invest., 115:2119-2127, August 2005)

報告日期: 2005/10/25
報告時間: 17:10/18:00
報告學生: 李崑豪
講評老師: 蔣輯武

Akt1/protein kinase Bα is critical for ischemic

and VEGF-mediated angiogenesis


J. Clin. Invest. 2005, 115:2119–2127


Speaker:李崑豪                       Time: Oct 25, 2005 ( ~ )

Commentator:蔣輯武 老師             Place: Classroom 602




Akt is originally identified as a cellular counterpart of the oncogene derived from murine AKT8 retrovirus. It is a serine/threonine protein kinase that is activated by a number of growth factors and cytokines in a phosphatidylinositol-3 kinase– dependent manner. Activation of the PI3K/Akt pathway accounts for many of the actions of angiogenic growth factors such as VEGF, including cell survival, migration, tube formation, and promotion of the release of NO in endothelial cells (ECs). And there are some reports that have described cardioprotective and antiapoptotic roles of Akt in different models of ischemia and hypoxia in vitro and in vivo. However, there is little direct genetic evidence supporting a role for Akt in regulating angiogenesis in vivo. In previous studies, they indicated that the Akt1-/- mice have smaller litter sizes, impaired extraembryonic vascular patterning and placental hypotrophy, reduced fetal weight, and a partially penetrant phenotype of a higher fetal mortality. In order to directly explore the roles of Akt isoforms during postnatal angiogenesis in the adult, the authors used mice deficient in either Akt1 or Akt2 and examined several angiogenic phenotypes in vivo. They show that Akt1, but not Akt2, mediates the angiogenic response to hind-limb ischemia and VEGF stimulation in vivo. Akt1 is required for the homing of endothelial precursor cells to areas of ischemia in vivo. Akt1 is also required for basal and agonist-mediated NO release from mouse lung endothelial cells (MLECs) and for the migration of MLECs and mouse lung fibroblasts in response to chemoattractants in vitro.




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