# Systems Biology of Angiogenesis in Peripheral Arterial Disease

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $812,408

## Abstract

SUMMARY
Peripheral arterial disease (PAD) is a major complication of systemic atherosclerosis. PAD afflicts over 8
million patients in the US and millions more around the world. Patients with PAD have problems from reduced
blood flow to the leg resulting from the arterial occlusions and they suffer high rates of stroke and heart attack.
There is a large unmet need for medical treatments to improve perfusion to treat PAD; currently, no medical
treatment effectively increases blood flow to the leg in PAD. Numerous clinical trials attempting to increase
angiogenesis have failed to provide long-lasting clinical improvements in PAD. In addition, the reason for the
high rates of heart attack, stroke, and death associated with PAD are only incompletely understood.
To meet this need for medical therapies to improve blood flow in PAD, we need a better understanding of what
controls angiogenesis in PAD. Our approach is to integrate detailed mechanistic multiscale computational
models with PAD-specific experimental data to simulate the pathophysiology and treatment of PAD.
This project is based on the proposition that therapeutic approaches in PAD will be realized by growing blood
vessels that are: stable, not leaky or malformed; and do not promote adverse inflammation. Therefore, we
hypothesize that a major focus of therapeutic strategies in PAD must be on promoting the growth of normal
blood vessels, including modulating immune cells for optimal angiogenesis. To advance the computational
framework for therapeutic angiogenesis, we will build an integrative signaling network that includes VEGFA
and its endothelial receptors VEGFR1, VEGFR2, and VEGFR3, co-receptors, and an associated pathway,
Angiopoietin (Ang)-Tie, that plays an important role in vascular leakage and vascular stability. Inflammation is a
hallmark of PAD and other ischemic diseases, and we will formulate experiment-based computational models
of macrophage polarization, and design and test strategies that can shift the system toward a pro-angiogenic,
pro-stability, non-leaky, and anti-inflammatory phenotype.
This project will result in predictive, experimentally-validated models of important signaling pathways, with
specific relevance to PAD. It will advance state of the art in modeling integrative interdependent signaling
pathways at the cellular and tissue levels. The project will lead to a better fundamental understanding of PAD
and its determinants and to translational applications.

## Key facts

- **NIH application ID:** 10368099
- **Project number:** 5R01HL101200-13
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ALEKSANDER S. POPEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $812,408
- **Award type:** 5
- **Project period:** 2010-04-13 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10368099

## Citation

> US National Institutes of Health, RePORTER application 10368099, Systems Biology of Angiogenesis in Peripheral Arterial Disease (5R01HL101200-13). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10368099. Licensed CC0.

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