# Vascular Basement Membrane Composition Regulates Pericyte Investment in Developing Blood Vessels

> **NIH NIH R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2022 · $389,131

## Abstract

PROJECT SUMMARY / ABSTRACT (DESCRIPTION)
Blood vessels deliver nutrients and oxygen throughout the body to sustain the health of every tissue and
organ. Many clinical diseases therefore arise from or directly affect the vascular system. Improved insight into
vessel growth and maintenance will guide the development of therapeutic strategies to treat debilitating and
often life-threatening illnesses associated with blood vessel abnormalities. Pericytes are perivascular cells that
wrap around and invest into growing blood vessels, providing essential regulation of vessel stability, maturity
and quiescence. Numerous pathologies such as neonatal intracranial hemorrhage, diabetic retinopathy,
Alzheimer's disease, and metastatic cancer are exacerbated by disrupted vascular function, and barrier
function in particular, resulting from defects in pericyte-endothelial cell interactions. Despite the importance of
pericyte-endothelial interactions in human health and disease, critical gaps in knowledge exist about the
mechanism by which pericytes are recruited to and retained at specific locations (i.e. invest) on developing
blood vessels. We and others have previously shown that the Vascular Endothelial Growth Factor-A (VEGF-A)
pathway, via one of its negative receptors Flt-1 (VEGF Receptor-1) – soluble Flt-1 (sFlt-1) in particular –
generates a spatial heterogeneity in endothelial cell phenotypes to promote efficient blood vessel formation
(i.e. “tip” cells sprout and form new vessel branches, “stalk” cells proliferate and contribute to vessel
elongation). Precisely how this endothelial phenotypic heterogeneity contributes to establishing these specific
sites for pericyte investment is not well defined. Moreover, the vascular basement membrane (vBM) mediates
pericyte-endothelial cell interactions during blood vessel formation, but it is not clear how the vBM components
Types III and IV Collagen (Col-III and Col-IV, respectively) modulate pericyte investment downstream of
VEGF-A signaling. The overall objective of this research is to investigate how Col-III and Col-IV deposition
between pericytes and endothelial cells is (i) regulated by VEGF-A signaling in endothelial cells but not
pericytes, and (ii) maintained at precise levels to promote and sustain pericyte investment. We will test this
hypothesis by combining innovative in vitro, ex vivo, and in vivo models with cutting-edge analytical
approaches to extend our preliminary observations showing that, when VEGF-A signaling is disrupted, pericyte
migration and investment along growing vessels decreases, and this decrease is associated with aberrant
deposition of Col-III and Col-IV, which appears to be a non-permissive substrate for pericyte adhesion and
migration. Collaborators will provide expertise in extracellular matrix (ECM) biology and in novel imaging
approaches that will be essential for thorough investigation of pericyte investment into the blood vessel wall.
Combining these innovative approaches,...

## Key facts

- **NIH application ID:** 10449094
- **Project number:** 5R01HL146596-04
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** John Christopher Chappell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $389,131
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449094

## Citation

> US National Institutes of Health, RePORTER application 10449094, Vascular Basement Membrane Composition Regulates Pericyte Investment in Developing Blood Vessels (5R01HL146596-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10449094. Licensed CC0.

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