# Endothelial Mechanotransduction in Thoracic Aneurysm Formation and Progression

> **NIH NIH P01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $443,154

## Abstract

Project Summary
This project is based on the view that aneurysms represent a pathological response to high wall strain in which
the artery wall thins and weakens instead of thickening and strengthening as it does in normal compensatory
artery wall remodeling. We hypothesize that inflammatory effects of endothelial cell responses to disturbances
in blood flow, and from altered signaling due to extracellular matrix remodeling are important drivers of this switch
from compensatory to pathological remodeling. The proposed experiments will test these hypotheses and
elucidate mechanisms that link inflammation to aneurysm initiation or progression. We will use two
complementary model systems. The first is Marfan syndrome (MFS) mice, which develop severe pathological
vascular remodeling and thoracic aortic aneurysms due to a defect in fibrillin 1. The second is continuous infusion
of two vasoconstrictors, which induce either compensatory vascular remodeling or moderate pathological
remodeling in response to elevated blood pressure. Comparison of these systems will therefore allow us to
identify differences between physiological and pathological remodeling of the aorta. Aim 1 will test the effects
of mutations in a critical flow-sensing gene that specifically abolish mechanotransduction pathways without
compromising overall functions (with Cores B and C). In Aim 2, we will test effects of mutations in integrins and
interacting molecules that specifically affect the inflammatory aspects of matrix remodeling (with Cores B and
C). In Aim 3, we will investigate the role of flow in regulating expression of Angiotensin II receptor 1, a well-
established mediator of aneurysm formation (with Project 1 and Cores B and C). We will also contribute
expertise in mechanotransduction to studies in Projects 1, 2 and 4. Results from these experiments will provide
an understanding of how specific inflammatory pathways contribute to thoracic aortic aneurysms (TAAs) and
thereby identify potential new targets for pharmacological intervention.

## Key facts

- **NIH application ID:** 10136699
- **Project number:** 5P01HL134605-04
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Martin A Schwartz
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $443,154
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136699

## Citation

> US National Institutes of Health, RePORTER application 10136699, Endothelial Mechanotransduction in Thoracic Aneurysm Formation and Progression (5P01HL134605-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10136699. Licensed CC0.

---

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