# Neovessel Guidance in Angiogenesis

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $437,466

## Abstract

SUMMARY
Neovessel guidance in angiogenesis Vascular connectivity between adjacent vessel beds within and between
tissue compartments is an essential aspect of any successful neovascularization process. To establish new
connections, growing neovessels must locate other vascular elements during angiogenesis, often crossing matrix
and other tissue-associated boundaries and interfaces. This is perhaps best highlighted in situations of tissue
grafting (e.g. tissue free flaps) during which the vasculature of the graft must cross the graft-host tissue interface
before connecting to the surrounding host circulation in order for the graft to survive. An inability for a tissue graft
vasculature to connect to the host vasculature is the primary cause for tissue graft failure and necrosis. How
growing neovessels traverse any tissue interface, whether part of the native tissue structure or secondary to a
grafting procedure, is not known. In a series of preliminary experiments, we have determined that actively
growing neovessels are unable to spontaneously cross a stroma-stroma interface during angiogenesis. Our
published findings that tissue stromal biomechanics, specifically the biophysical aspects of the matrix, has a
profound influence on the direction and branching of growing neovessels suggests that this interface is
biomechanically incompatible with interface invasion. In addition, we have evidence that a sub-population of
tissue-resident, stromal macrophages facilitates neovessel invasion of the stromal interface during angiogenesis
through a VEGF-A-dependent process. Importantly, it appears that stromal cells need to migrate across the
interface in order to promote interface invasion by the neovessels, suggesting that spatial gradients of VEGF-A
are required. Based on these observations, we hypothesize that the graded angiogenic factor signals overcome
the biomechanical barriers to directed angiogenesis caused by a stroma-stroma interface to promote interface
neovascular invasion. The project will involve a combination of in vitro and computational models of angiogenesis
across tissue-tissue boundaries to test this hypothesis and determine the mechanism by which stromal cells use
VEGF-A signaling to regulate neovessel behavior in coordination with stroma biomechanical dynamics. These
studies will provide new insights into a poorly understood aspect of vascular biology and tissue-vascular
dynamics as well as create opportunities for therapeutic strategies to facilitate tissue healing, improving
angiogenesis-based treatments, and tissue grafting/transplantation.

## Key facts

- **NIH application ID:** 9841967
- **Project number:** 5R01HL131856-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** JAMES B HOYING
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $437,466
- **Award type:** 5
- **Project period:** 2016-12-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841967

## Citation

> US National Institutes of Health, RePORTER application 9841967, Neovessel Guidance in Angiogenesis (5R01HL131856-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9841967. Licensed CC0.

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