Changes in Hemodynamics by Time-Lapse Microscopy during Embryonic Development

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The cardiovascular system adapts to physiological needs by remodeling the vasculature. Vascular remodeling involves both the formation of new blood vessels, called angiogenesis, and changes in diameter of existing blood vessels, called arteriogenesis. Vascular remodeling is an important therapeutic target. When a blood vessel becomes occluded, such as occurs during a stroke or a heart attack, the network of blood vessels must undergo vascular remodeling in order to restore blood flow. One of the most important cues for vascular remodeling is the blood flow itself. Blood flow creates a mechanical force on the vessel wall called wall shear stress and the cells that line the blood vessel wall can sense wall shear stress. This aim of this proposal is to study the effect of wall shear stress on angiogenesis and arteriogenesis. We propose using the avian embryo as our model. When blood flow starts in the embryo, the blood vessels undergoes significant remodeling both by angiogenesis and by arteriogenesis. The advantage of the embryo is that it is much simpler system and furthermore, we can image both the fluid dynamics and the changes in the blood vessels in real-time using embryo culture on a microscope stage. We will therefore culture embryos on a microscope stage and look at vascular proliferation, migration of vascular cells, changes in vessel diameter and the sprouting of new vessels in relationship to the amount of wall shear stress present. We will also uses computational techniques to analyse the flow patterns that are present during remodeling in more detail. The students who are trained under this research program will develop advanced knowledge of fluid dynamics as well as learning in vivo imaging techniques that are highly sought after.