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 Scopus citations

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)173-190
Number of pages18
JournalAngiogenesis
Volume19
Issue number2
DOIs
StatePublished - Apr 1 2016

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cancer Research

Fingerprint Dive into the research topics of 'Rasip1 is essential to blood vessel stability and angiogenic blood vessel growth'. Together they form a unique fingerprint.

  • Cite this