# Characterization of Altered Mechanosensing in Mouse Models of ECM-induced TAA

> **NIH NIH P01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $443,886

## Abstract

Project summary
Thoracic aortic aneurysms (TAAs) are a group of life-threatening conditions driven by complex
pathophysiological interactions among different cell types, distinct extracellular matrix (ECM) compartments
and multiple biochemical signals that, together, predispose the vessel wall to dissection and rupture. We
hypothesize that, irrespective of the underlying cause, dysfunctional mechanobiology is a shared mechanism
of TAA development and consequently, that molecules sensing, transducing or countering mechanical stress
may represent potential new targets for drug therapy. This PPG focuses on identifying key disease-related
cellular responses that are triggered either by experimentally increased blood pressure on a structurally normal
tissue or by physiological hemodynamic load on a genetically deficient matrix. Project 1 employs a mouse
model of progressively severe Marfan syndrome (MFS) to characterize the latter mechanism of arterial
disease. This genetic model of TAA was chosen because the mutated protein (fibrillin-1) regulates several key
aspects of arterial function and homeostasis, including tissue integrity, endothelial cell mechanotransduction,
angiotensin II (AngII) type I receptor (AT1r) activity and TGFβ signaling. Our proposal is organized into two
specific aims that combine genetic, biomechanical and computational approaches to elucidate the primary
triggers and downstream mediators and targets of AngII-dependent and AngII-independent AT1r signaling in
distinct aortic compartments of MFS mice (Aim 1), and to evaluate how incremental loss of ECM integrity
influences the biological responses of aortic cells to induced hypertension (Aim 2). Expected findings will
inform, extend or complement the studies pursued by other PPG projects, which collectively will provide a new
tissue-level understanding of the molecular factors and cellular events responsible for TAA onset and
progression in a validated mouse model of lethal MFS.

## Key facts

- **NIH application ID:** 10378124
- **Project number:** 5P01HL134605-05
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Francesco B Ramirez
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $443,886
- **Award type:** 5
- **Project period:** 2018-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378124

## Citation

> US National Institutes of Health, RePORTER application 10378124, Characterization of Altered Mechanosensing in Mouse Models of ECM-induced TAA (5P01HL134605-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10378124. Licensed CC0.

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