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Lab Chip. 2012 Dec 7;12(23):5000-6. doi: 10.1039/c2lc40389g.

RhoA mediates flow-induced endothelial sprouting in a 3-D tissue analogue of angiogenesis.

Author information

  • 1Edwin L. Steele Laboratory for Tumour Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

Abstract

Endothelial cells (ECs) integrate signals from the local microenvironment to guide their behaviour. RhoA is involved in vascular endothelial growth factor (VEGF)-driven angiogenesis, but its role in mechanotransduction during sprouting has not been established. Using dominant negative cell transfections in a microfluidic device that recapitulates angiogenic sprouting, we show that endothelial cells respond to interstitial flow in a RhoA-dependent manner while invading a 3-D extracellular matrix. Furthermore, RhoA regulates flow-induced, but not VEGF gradient-induced, tip cell filopodial extensions. Thus, RhoA pathways mediate mechanically-activated but not VEGF-induced endothelial morphogenesis.

PMID:
23073300
PMCID:
PMC3490212
DOI:
10.1039/c2lc40389g
[PubMed - indexed for MEDLINE]
Free PMC Article
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