# Blood flow and structural adaptation in microcirculation

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2020 · $191,875

## Abstract

BLOOD FLOW AND STRUCTURAL ADAPTATION IN MICROCIRCULATION
PROJECT SUMMARY
Angiogenesis (growth of new blood vessels) is central to a wide range of physiological and pathological
processes, including development, growth, exercise, estrus cycle, wound healing, collateral formation following
ischemia, neovascular macular degeneration, and tumor growth. Much research on angiogenesis has focused
on the cellular and molecular processes of vessel formation. How networks with adequate functional properties
are formed, through angiogenesis, adaptation (remodeling) and pruning (removal) of vessels, has received
less attention. This project uses theoretical models to address the following question: How do the processes
of angiogenesis, structural adaptation and pruning generate vascular structures that meet the
functional needs of the tissue? The developing retina of the neonatal mouse is used extensively as an
animal model for studying angiogenesis. After birth, the retinal microcirculation spreads rapidly by sprouting
angiogenesis to form a primary plexus covering the inner surface of the retina by P9 (postnatal day 9). During
P8 to P14, sprouts from this network dive into the retina, forming new networks at two different levels within the
retina. The availability of a large amount of data from this well-characterized experimental system provides a
strong basis for developing detailed theoretical models, and for using these models to determine the roles of
specific biological mechanisms in the formation of functional network structures. Specific Aim 1 is to develop
two-dimensional models for the growth of the primary retinal plexus during P1-P9. A segment-based
approach will be used to describe network structure, growth, adaptation and pruning, and continuous field
models will be used for oxygen and growth factor diffusion. The following biological mechanisms will be
included: production of growth factors in hypoxic regions; stimulation of sprouting angiogenesis by growth
factors; lateral inhibition of tip cell formation to control sprout density; growth of sprouts led by endothelial tip
cells; guidance of sprouts by the preexisting network of astrocytes; structural adaptation of vessel diameters in
response to wall shear stress, pressure, metabolic conditions and conducted responses; and pruning of
redundant vessels. The questions to be addressed are: What is the role and importance of each of these
biological mechanisms? What are the effects of its modulation or abolition? Model predictions will be compared
with observations in wild-type and genetically modified animals. Specific Aim 2 is to develop three-
dimensional models for the growth of the deeper plexuses and the regression of the primary plexus
during P8-P14. The modeling approach will be extended to three dimensions. Effects of variations in oxygen
and growth factor levels through the retina will be included. These studies will provide insight into the
mechanisms by which functional vascular net...

## Key facts

- **NIH application ID:** 9903421
- **Project number:** 5R01HL034555-35
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Timothy W. Secomb
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,875
- **Award type:** 5
- **Project period:** 1985-07-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9903421

## Citation

> US National Institutes of Health, RePORTER application 9903421, Blood flow and structural adaptation in microcirculation (5R01HL034555-35). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9903421. Licensed CC0.

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