Details

Autor(en) / Beteiligte

• Chang, Andrew H
• Raftrey, Brian C
• D'Amato, Gaetano
• Surya, Vinay N
• Poduri, Aruna
• Chen, Heidi I
• Goldstone, Andrew B
• Woo, Joseph
• Fuller, Gerald G
• Dunn, Alexander R
• Red-Horse, Kristy

Titel

DACH1 stimulates shear stress-guided endothelial cell migration and coronary artery growth through the CXCL12-CXCR4 signaling axis

Ist Teil von

• Genes & development, 2017-07, Vol.31 (13), p.1308-1324

Ort / Verlag

United States: Cold Spring Harbor Laboratory Press

Erscheinungsjahr

2017

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Sufficient blood flow to tissues relies on arterial blood vessels, but the mechanisms regulating their development are poorly understood. Many arteries, including coronary arteries of the heart, form through remodeling of an immature vascular plexus in a process triggered and shaped by blood flow. However, little is known about how cues from fluid shear stress are translated into responses that pattern artery development. Here, we show that mice lacking endothelial had small coronary arteries, decreased endothelial cell polarization, and reduced expression of the chemokine Under shear stress in culture, overexpression stimulated endothelial cell polarization and migration against flow, which was reversed upon CXCL12/CXCR4 inhibition. In vivo, DACH1 was expressed during early arteriogenesis but was down in mature arteries. Mature artery-type shear stress (high, uniform laminar) specifically down-regulated DACH1, while the remodeling artery-type flow (low, variable) maintained DACH1 expression. Together, our data support a model in which DACH1 stimulates coronary artery growth by activating expression and endothelial cell migration against blood flow into developing arteries. This activity is suppressed once arteries reach a mature morphology and acquire high, laminar flow that down-regulates DACH1. Thus, we identified a mechanism by which blood flow quality balances artery growth and maturation.