Endothelial Mechanotaxis During Development

University Of California, San Diego, La Jolla CA

Investigators

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Abstract

? DESCRIPTION (provided by applicant): Formation of blood vasculature is a complicated process requiring both genetic and environmental input. Failure in vascular development is a major cause of congenital birth diseases. The most important environmental factor controlling vascular remodeling is blood flow which has an ability to change the identity of vessels, and critical in regulation of formations of interconnections between the primary network and secondary sprouts. Understanding the mechanism by which vasculature adapts to changes in blood flow perfusion is of critical scientific and clinical importance. Endothelial cells form the interface between blood and underlying tissues, and are usually thought of as motionless unless there is tissue injury or angiogenesis. However, I made a novel and unexpected finding that endothelial cells migrate centrifugally in venous circulation, a process that is likely to influenc vascular patterning. Moreover, I have developed new microfluidic devices that allow me to study endothelial cells under a wide variety of flow conditions. I propose to investigate mechanosensing mechanisms by which flow directs endothelial cell migration and to determine the role of this migration in vascular development.