# Co-regulation of developmental vascular anomalies by fibronectin and collagen

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2020 · $192,500

## Abstract

Project Summary
The term vascular anomaly encompasses a broad spectrum of diseases, including the extremely common
vasoproliferative disorder infantile hemangioma, and more rare pathologies such as cerebral cavernous
malformation. Together, these diseases are estimated to affect more than 10% of the world’s population, and
most often occur in children under the age of 5. Several forms of vascular anomalies exhibit an increase in
expression of the extracellular matrix protein fibronectin, despite their cause being traced to disparate genetic
mutations. Normal adult vascular basement membrane is comprised mainly of laminin and collagen and lacks
fibronectin. Thus, the presence of fibronectin in infantile hemangioma, cavernous angioma/cerebral cavernous
malformation, Sturge-Weber associated hemangioma, and VHL-disease associated hemangioma, among
others, could contribute to a heretofore unidentified pathological mechanism. Fibronectin can stimulate
endothelial proliferation and neo-angiogenesis in vitro, however, the role of fibronectin in the pathogenesis of
vascular malformations has not been directly determined. Of the many cellular interactions mediated by
fibronectin, its interaction with collagen is one of the least understood. Fibronectin and collagen appear to act
synergistically to promote angiogenesis, and our new preliminary data show that blocking this interaction
inhibits angiogenic tube formation. As the interaction between fibronectin and collagen has not been studied in
an endothelial context, several fundamental questions remain about the role of this interaction in normal
endothelial cells and in the development of vascular anomalies. Thus, we hypothesize that the
fibronectin/collagen interaction regulates neo-angiogenesis and contributes to the formation of vascular
anomalies. In this proposal, we will determine the contribution of fibronectin/collagen binding to matrix
deposition and stability in endothelial cell cultures, and how this interaction regulates the formation of new
vessels in vitro and in vivo by examining whether a peptide inhibitor of this interaction, R1R2, reduces the
presence of collagen in the matrix, increases collagen internalization, and inhibits tube formation in vitro and
new vessel growth in vivo. In addition, we will determine whether fibronectin/collagen binding contributes to the
abnormal vessel formation in mouse models of cerebral cavernous malformation and hemangioma. Together,
these data will determine the role of the fibronectin/collagen interaction in normal angiogenesis and the
development of vascular anomalies, provide proof-of-principle that a common mechanism underlies the
pathogenesis of vascular anomalies, and support further studies of R1R2 as a therapeutic agent.

## Key facts

- **NIH application ID:** 9921446
- **Project number:** 5R21HD098576-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Angela J Glading
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2019-05-01 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9921446

## Citation

> US National Institutes of Health, RePORTER application 9921446, Co-regulation of developmental vascular anomalies by fibronectin and collagen (5R21HD098576-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9921446. Licensed CC0.

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