# ECM and shear stress

> **NIH NIH P01** · YALE UNIVERSITY · 2022 · $520,474

## Abstract

Poor arteriogenesis, in which blood vessels parallel to an arterial blockage fail to remodel to restore
blood flow to the affected tissue, is a major factor in illness and death in peripheral and coronary artery
disease. This project is based on the hypothesis that arteriogenesis is initiated by elevated shear stress
in small blood vessels that triggers a sequence of endothelial activation, inflammation, matrix
remodeling, vessel expansion and resolution, which returns shear levels toward normal and restores
normal vessel function. Artery remodeling is thus governed by a fluid shear stress set point such that
when shear stress goes above or below the optimal range, ECs trigger a response to change vessel
diameter and return shear toward the original value. The overall goal of this grant is to elucidate these
mechanisms in more detail and identify restriction points that inhibit arteriogenesis in disease. Our
preliminary and published data implicate extracellular matrix remodeling and smad activation as key
components of these processes. Based on these results, we will: 1) Elucidate the role of matrix
remodeling in arteriogenesis, specifically examining whether blocking a link between fibronectin and
inflammatory pathways improve arteriogenesis in disease models.
2) Elucidate the signaling networks that govern the fluid shear stress set point. 3) Develop antibodybased
tools that specifically alter the effects of flow on activation of Smad 2/3 vs Smad 1/5/8, and
test their effects on arteriogenesis.

## Key facts

- **NIH application ID:** 10433820
- **Project number:** 5P01HL107205-10
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Martin A Schwartz
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $520,474
- **Award type:** 5
- **Project period:** 2012-02-10 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10433820

## Citation

> US National Institutes of Health, RePORTER application 10433820, ECM and shear stress (5P01HL107205-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10433820. Licensed CC0.

---

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