RhoA mediates flow-induced endothelial sprouting in a 3-D tissue analogue of angiogenesis.
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.
Edwin L. Steele Laboratory for Tumour Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Jonathan W
JW
Song
Julien
J
Daubriac
Janet M
JM
Tse
Despina
D
Bazou
Lance L
LL
Munn
D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D013314:Stress, Mechanical; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; D020742:rhoA GTP-Binding Protein