Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo

Nat. Med. 11, 1188-1196 (2005)

Speaker: 林怜伶                        Date:03/29/2006 14:00-15:00

Commentator:周楠華醫師                 Place: 601教室

Abstract:

Akt, or protein kinase B, is a multifunctional serine-threonine protein kinase implicated in a diverse range of cellular functions including cell metabolism, survival, migration, and gene expression. It has been proposed as promising target for treatment of angiogenesis-dependent pathologies, such as cancer and ischemic injury.¹ But its precise role in neovascularization remain elusive. The authors show that Akt1 is the predominant isoform in vascular cells and describe the unexpected consequences of Akt1 knockout on vascular integrity and pathological angiogenesis. In three distinct in vivo models, they observe that angiogenic responses were enhanced in Akt1^-/- mice; these enhanced responses were associated with impairment of blood vessel maturation and increased vascular permeability. The major phenotypic changes in vascular permeability and angiogenesis were linked to reduced expression of two endogenous vascular regulators, thrombospondins 1 (TSP-1) and 2 (TSP-2). They establish a crucial role of an Akt-thrombospondin axis in angiogenesis.²As neoangiogenesis and vascular leakage are important pathophysiological features of cancer, ischemic injury, inflammation and degenerative disorders, these findingshave broad therapeutic implications.

References:

1.    Ackah, E. et al. Akt1/protein kinase Balpha is critical for ischemic and VEGF-mediated angiogenesis. J. Clin. Invest. 115, 2119–2127 (2005).

2.    Chen, J. et al. Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo. Nat. Med. 11, 1188-1196 (2005).