# Investigation of hepatic factor in pulmonary arteriovenous malformations

> **NIH NIH K08** · MEDICAL COLLEGE OF WISCONSIN · 2022 · $150,352

## Abstract

PROJECT SUMMARY
The proposed studies in this K08 application will use innovative approaches to investigate soluble vascular
endothelial growth factor receptor 1 (sVEGFR1) as a critical regulator of pulmonary microvascular remodeling
and inhibitor of pulmonary arteriovenous malformation (PAVM) development. Vascular endothelial growth
factor (VEGF) signaling is integral to sprouting angiogenesis and vascular homeostasis. If left unchecked,
VEGF signaling can also lead to vascular instability and pathologic remodeling. Inhibiting VEGF signaling in
multiple vascular beds can normalize existing AVMs, and supplemental sVEGFR1 can prevent brain AVMs.
Using patient blood samples, we recently identified that sVEGFR1 is significantly elevated in hepatic vein
serum and may be a potential inhibitor of PAVM formation in patients with univentricular congenital heart
disease. The aims of this proposal will directly test our preliminary observation by examining patient blood
samples and testing the effects of sVEGFR1 on the pulmonary microvasculature in vitro, ex vivo, and in vivo.
The aims of this proposal are prerequisites to advancing the care of patients with univentricular congenital
heart disease and PAVMs. These aims will also improve our understanding of pulmonary microvascular
biology.
The training plan in this K08 application will support my career development with two main goals. First, I will
further develop expertise manipulating patient-derived and biologically relevant tissues in vitro and ex vivo to
investigate lung endothelial cell gene expression, angiogenesis, and microvascular remodeling. Using
molecular biology tools to modify variables in vitro and probe clinically oriented questions will allow me to
achieve the objectives of this proposal and address new questions in the future as a physician-scientist.
Second, I will acquire new skills and experience working with transgenic animal models and innovative
techniques to study the lung microvasculature. The ability to adeptly use modern transgenic animal models, as
well as leverage clinical skills to modify animal physiology, will position me to independently investigate clinical
problems. Experience with advanced experimental techniques, such as precision cut lung slices, isolated lung
perfusion, and next-generation sequencing (RNA-seq and single cell RNA-seq), will allow me to test
hypotheses with innovative scientific approaches. Finally, as a physician-scientist these skills will position me
well to collaborate with investigators locally and outside my institution to advance team science.

## Key facts

- **NIH application ID:** 10448051
- **Project number:** 1K08HL157510-01A1
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Andrew D Spearman
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $150,352
- **Award type:** 1
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448051

## Citation

> US National Institutes of Health, RePORTER application 10448051, Investigation of hepatic factor in pulmonary arteriovenous malformations (1K08HL157510-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10448051. Licensed CC0.

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