# Flow regulation of the Alk1/Eng pathway in vascular homeostasis and disease

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $743,519

## Abstract

PROJECT SUMMARY
Fluid shear stress-dependent vessel remodeling is an essential regulatory mechanism in embryonic
development and in adult vascular homeostasis where it optimizes blood flow to target tissues. Conversely, un-
or mis-regulated remodeling results in vascular malformations, while poor remodeling is a key aspect of blood
flow restriction in coronary and periphery artery disease. Our preliminary data reveal the existence of a regulatory
network with two mutually inhibitory states, one associated with vessel stability and one with physiological
outward remodeling or pathological AVM formation. These results allow us to propose a unifying hypothesis that
links physiological and pathological remodeling, and suggest the existence of control points that can be
manipulated to either increase or decrease vascular lumen diameter. The project aims to elucidate these
regulatory mechanisms and then harness these new insights to investigate their relevance to vascular
development, to identify therapeutic targets for HHT patients who suffer from excessive pathological remodeling,
and identify therapeutic targets for coronary and peripheral artery disease patients where physiological
remodeling is impaired. We will define the molecular basis of this novel EC shear stress mechanism, determine
its biological role and develop and test therapeutic applications based on this knowledge.

## Key facts

- **NIH application ID:** 10881956
- **Project number:** 5R01HL169510-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Anne Christine Eichmann
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $743,519
- **Award type:** 5
- **Project period:** 2023-07-15 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881956

## Citation

> US National Institutes of Health, RePORTER application 10881956, Flow regulation of the Alk1/Eng pathway in vascular homeostasis and disease (5R01HL169510-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10881956. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*