The Hoying Laboratory, researching cardiovascular therapeutics and regenerative medicine.
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  Research >> microvascular reconstruction  
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The mammalian vasculature is a complex and dynamic tissue system that performs a broad array of activities. Comprised of a collection of very heterogeneous blood vessels organized into a sophisticated network, the vasculature serves as the primary means by which different tissues and organs are supplied with blood and integrated. As part of this network, the blood vessels, which can be highly specialized, are able to make rapid and lasting changes in structure and function. This is no less evident than during tissue vascularization in which distal regions of the vasculature, the microvasculature, expands and adapts to meet new needs in function.

In the simplest sense, vascularization is the process by which perfusion pathway length and vessel number are increased (via angiogenesis) and organized (via network remodeling) into a functional vascular bed. The effective expansion of a microvascular bed requires the newly formed vessels to progress from a disordered collection of neovessels into an organized network of perfused vessels to maintain health. This transition from angiogenesis to a functional circulation involves differentiation of neovessels into functional vessel types and organization of these vessels into a vascular tree. This maturation of the network involves further refinement of vessel elements into larger and smaller caliber vessels, longer and smaller vessel segment lengths and vessel removal. Ultimately, these structural changes in vessels lead to long-term adjustments in blood flow resistance and flow pathways in the vasculature.

Despite the current understanding of events and processes that lead to new vessel growth, we know little about the control mechanisms that regulate those vascular activities following progression from angiogenesis to network maturity. In particular, we do not know what molecular “rules” govern the events following angiogenesis such as how a vessel segment establishes position and identity within the larger network of vessels comprising the new microvascular bed. Using molecular, cellular, physiological, and genomic experimental approaches in combination with applied scientists, bioengineers and mathematicians, we are working to define the determinants of post-angiogenesis vascular form and function in the microcirculation. What we are learning is being incorporated into strategies and technologies intended to reconstruct the microvasculature in a variety of diseases.

 

 
day7 ink perfused fragment construct

day 28 ink perfused mcrovessel network

Ink castings of new and mature microcirculations. We are researching the mechanism by which newly formed vessels (top panel) progress into a mature vasculature (bottom panel).

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Hoying Lab >> Research
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Cardiovascular Innovation Institute