Rasip1 is essential to blood vessel stability and angiogenic blood vessel growth

Yeon Koo, David M. Barry, Ke Xu, Keiji Tanigaki, George E. Davis, Chieko Mineo, Ondine Cleaver

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Abstract: Cardiovascular function depends on patent, continuous and stable blood vessel formation by endothelial cells (ECs). Blood vessel development initiates by vasculogenesis, as ECs coalesce into linear aggregates and organize to form central lumens that allow blood flow. Molecular mechanisms underlying in vivo vascular ‘tubulogenesis’ are only beginning to be unraveled. We previously showed that the GTPase-interacting protein called Rasip1 is required for the formation of continuous vascular lumens in the early embryo. Rasip1−/− ECs exhibit loss of proper cell polarity and cell shape, disrupted localization of EC–EC junctions and defects in adhesion of ECs to extracellular matrix. In vitro studies showed that Rasip1 depletion in cultured ECs blocked tubulogenesis. Whether Rasip1 is required in blood vessels after their initial formation remained unclear. Here, we show that Rasip1 is essential for vessel formation and maintenance in the embryo, but not in quiescent adult vessels. Rasip1 is also required for angiogenesis in three models of blood vessel growth: in vitro matrix invasion, retinal blood vessel growth and directed in vivo angiogenesis assays. Rasip1 is thus necessary in growing embryonic blood vessels, postnatal angiogenic sprouting and remodeling, but is dispensable for maintenance of established blood vessels, making it a potential anti-angiogenic therapeutic target.Graphical Abstract: [Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)1-18
Number of pages18
JournalAngiogenesis
DOIs
StateAccepted/In press - Feb 20 2016

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Blood vessels
Blood Vessels
Endothelial cells
Growth
Endothelial Cells
Embryonic Structures
Maintenance
GTP Phosphohydrolases
Retinal Vessels
Cell Polarity
Cell Shape
Assays
Blood
Adhesion
Extracellular Matrix
Cultured Cells
Defects
Proteins

Keywords

  • Angiogenesis
  • Blood vessel
  • Endothelial
  • Lumen
  • Rasip1
  • Tubulogenesis
  • Vascular
  • Vasculogenesis
  • VE-cadherin

ASJC Scopus subject areas

  • Cancer Research
  • Physiology
  • Clinical Biochemistry

Cite this

Rasip1 is essential to blood vessel stability and angiogenic blood vessel growth. / Koo, Yeon; Barry, David M.; Xu, Ke; Tanigaki, Keiji; Davis, George E.; Mineo, Chieko; Cleaver, Ondine.

In: Angiogenesis, 20.02.2016, p. 1-18.

Research output: Contribution to journalArticle

Koo, Yeon ; Barry, David M. ; Xu, Ke ; Tanigaki, Keiji ; Davis, George E. ; Mineo, Chieko ; Cleaver, Ondine. / Rasip1 is essential to blood vessel stability and angiogenic blood vessel growth. In: Angiogenesis. 2016 ; pp. 1-18.
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