Issue 23, 2012
From the journal:

Lab on a Chip

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

Jonathan W. Song,a   Julien Daubriac,a   Janet M. Tse,a   Despina Bazoua  and  Lance L. Munn*a  

* Corresponding authors

a Edwin L. Steele Laboratory for Tumour Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
E-mail: munn@steele.mgh.harvard.edu

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.

Graphical abstract: RhoA mediates flow-induced endothelial sprouting in a 3-D tissue analogue of angiogenesis

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Article information

DOI
https://doi.org/10.1039/C2LC40389G
Article type
Paper
Submitted
22 Apr 2012
Accepted
24 Sep 2012
First published
26 Sep 2012

Lab Chip, 2012,12, 5000-5006

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

J. W. Song, J. Daubriac, J. M. Tse, D. Bazou and L. L. Munn, Lab Chip, 2012, 12, 5000 DOI: 10.1039/C2LC40389G

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