R-Ras-Akt axis induces endothelial lumenogenesis and regulates the patency of regenerating vasculature

Research output: Contribution to journalArticle

Abstract

The formation of endothelial lumen is fundamental to angiogenesis and essential to the oxygenation of hypoxic tissues. The molecular mechanism underlying this important process remains obscure. Here, we show that Akt activation by a Ras homolog, R-Ras, stabilizes the microtubule cytoskeleton in endothelial cells leading to endothelial lumenogenesis. The activation of Akt by the potent angiogenic factor VEGF-A does not strongly stabilize microtubules or sufficiently promote lumen formation, hence demonstrating a distinct role for the R-Ras-Akt axis. We show in mice that this pathway is important for the lumenization of new capillaries and microvessels developing in ischemic muscles to allow sufficient tissue reperfusion after ischemic injury. Our work identifies a role for Akt in lumenogenesis and the significance of the R-Ras-Akt signaling for the patency of regenerating blood vessels.

Original languageEnglish (US)
Article number1720
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

Fingerprint

lumens
Microtubules
Chemical activation
activation
Tissue
angiogenesis
Oxygenation
Angiogenesis Inducing Agents
oxygenation
blood vessels
Endothelial cells
Blood vessels
muscles
Microvessels
Cytoskeleton
Vascular Endothelial Growth Factor A
Reperfusion
Blood Vessels
mice
Muscle

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

R-Ras-Akt axis induces endothelial lumenogenesis and regulates the patency of regenerating vasculature. / Li, Fangfei; Sawada, Junko; Komatsu, Masanobu.

In: Nature Communications, Vol. 8, No. 1, 1720, 01.12.2017.

Research output: Contribution to journalArticle

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