Microvascular growth and remodeling impact many tissue repair processes in the adult organism and play a critical role in a number of human diseases, including systemic arterial hypertension, chronic wounds, and ischemic disorders of the lower limbs and coronary circulations. The formation of a functional vascular network relies on specification of vessel types, including arterioles, capillaries, and venules, as well as their appropriate connectivity. Studies conducted on developing vascular networks have provided insight into how arterial/venous (A/V) polarity is established in the embryo and how A/V polarity impacts the growth process. However, the mechanisms by which A/V polarity in the adult microvasculature influence remodeling are currently not understood. Because proper vessel specification and connectivity is critical in driving normal microvascular function, we propose to test the hypothesis that molecules differentially present on arterioles and venules mediate adult microvascular remodeling.
Specific Aim 1 will quantify the spatial expression profile of NG2 in relation to other cell surface markers of A/V polarity (EphB4 and ephrinB2) in quiescent and remodeling adult microvascular networks.
Specific Aim 2 will determine if A/V specific expression of NG2 is a functional regulator of microvascular remodeling by disrupting NG2 signaling using a function-blocking antibody and using the NG2 -/- mouse.
Specific Aim 3 will determine if NG2 expression is dysregulated with respect to A/V polarity in a model of delayed wound healing (the diabetic mouse), and if blocking or eliminating NG2 function contributes to delayed wound healing.
These aims have the potential to enhance public health by 1) identifying novel vessel-specific targets for re-vascularization therapies and, 2) generating new methods for engineering organized vascularized constructs that can recover diseased or wounded tissues by stimulating new blood vessel growth.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL082838-05
Application #
8116996
Study Section
Hypertension and Microcirculation Study Section (HM)
Program Officer
Thrasher, Terry N
Project Start
2007-09-28
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2013-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$364,684
Indirect Cost
Name
University of Virginia
Department
Biomedical Engineering
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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Walpole, Joseph; Mac Gabhann, Feilim; Peirce, Shayn M et al. (2017) Agent-based computational model of retinal angiogenesis simulates microvascular network morphology as a function of pericyte coverage. Microcirculation 24:
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Mendel, Thomas A; Clabough, Erin B D; Kao, David S et al. (2013) Pericytes derived from adipose-derived stem cells protect against retinal vasculopathy. PLoS One 8:e65691

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