# Angiogenesis in Wound Repair

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $403,434

## Abstract

In skin wounds, angiogenesis is characterized by the abundant growth of new capillaries, ultimately creating a
vascular bed that is several times denser than normal tissue. As the wound resolves, most of these excess
vessels are removed, and the vascular content returns to a near normal state. While it has long been assumed
that a high level of capillary growth is essential for optimal healing, recent studies by us and others challenge
that notion. Our data suggests that normally healing wounds exhibit an overly robust and largely dysfunctional
angiogenic response that has detrimental effects on repair outcomes. Our work demonstrates that
pharmacologic treatments that establish a more refined and immediately functional vasculature improve
healing and reduce scar formation. A possible mechanism by which the normally vigorous angiogenic
response might spur scarring and fibrosis in wounds is via apoptotic endothelial cells. During wound resolution,
a substantial apoptotic endothelial cell load is created when capillaries are pruned back to normal levels. Our
preliminary data shows that apoptotic endothelial cells (EC) can directly influence fibroblast function, thereby
connecting vascular overgrowth, vascular regression, EC apoptotic load, and scar formation. The central
concept that underpins this application is that pharmacologic treatments that force the rapid development of a
mature vasculature support ideal healing, in part by reducing the apoptotic EC load. Aim 1 will advance toward
clinical trials by a) assessing the effect of a pharmacologic reduction of angiogenesis in a clinically relevant
rabbit model of hypertrophic scar formation, and b) surveying vascular content and maturity in human scar
tissues. Aims 2 and 3 address the central hypothesis that apoptotic EC directly influence wound resolution and
outcomes. Aim 2 will identify factors produced by apoptotic EC that provoke wound fibrosis. Aim 3 will
examine how apoptotic EC are cleared from wounds, and will establish how engulfment of apoptotic EC bodies
affects wound resolution. The proposed work is innovative because it addresses the unique clinical approach
of down-regulating the angiogenic response in wounds to reduce scar formation. Further innovation comes
from the examination of the influence of apoptotic EC, as the effect of the considerable endothelial apoptotic
load that occurs during wound resolution is almost entirely unstudied. The significance of this research lies in
the potential application to the clinical problems of hypertrophic scars and other fibrotic diseases. The findings
will support our long term goal of understanding the regulation of wound angiogenesis in health and disease,
and of capitalizing upon this knowledge to improve wound healing outcomes.

## Key facts

- **NIH application ID:** 9986771
- **Project number:** 5R01GM050875-27
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** LUISA A DIPIETRO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $403,434
- **Award type:** 5
- **Project period:** 1994-12-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986771

## Citation

> US National Institutes of Health, RePORTER application 9986771, Angiogenesis in Wound Repair (5R01GM050875-27). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9986771. Licensed CC0.

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