# Altered Mechanotransduction as a Therapeutic Target for Thoracic Aortic Aneurysm

> **NIH NIH P01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $2,400,712

## Abstract

Overall - Project Summary
Thoracic aortic aneurysms (TAA) are a group of life threatening conditions for which there is no good therapy.
We have proposed that specific genetic defects and environmental insults that alter distinct aspects of the
physiological interactions amongst cells and ECM lead to TAAs. As such, we view TAA as a disease of
altered vascular mechanobiology. In this Program Project Grant application, we will focus on the biological
responses of aortic cells, namely smooth muscle cells (SMC) and endothelial cells (EC) to the two major
physical determinants of disease, namely decreased ECM integrity and increased hemodynamic loads. We will
examine responses of ECs and SMCs during aneurysm development in mice with normal or compromised
ECM while focusing on signaling through angiotensin II and transforming growth factor beta in response to
increased hemodynamic loads. We will examine responses of the multiple mouse models to changes in flow,
pressure, and additional genetic perturbations focusing on AT1r, TGFBR1/2, TGFβ, and flow-dependent
signaling and activation (e.g., VECAD and PECAM). Consequences of cellular and tissue changes will be
analyzed with our Computational and Experimental Biomechanical Assessment and Bioinformatics and
Modeling Cores. For example, a subset of mice from all mouse models will be tested in the Computational and
Experimental Biomechanical Assessment core for biomechanical parameters and all differentially expressed
gene data from RNAseq experiments will be analyzed in the Bioinformatics and Modeling core. In this way the
information from all four projects can be applied en mass yielding considerably more significance. Our intent is
to develop novel interpretations from the changes in biomechanics and cell signaling to yield new testable
hypothesis concerning ECM modulation in addition to the revelation of important signaling nodes and novel
potential drug therapies. We propose that a consistent, integrated approach, using unique but complementary
mouse models for aneurysm genesis and progression, studied under several conditions will yield unique
insights in a synergistic manner.

## Key facts

- **NIH application ID:** 9883023
- **Project number:** 5P01HL134605-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** DANIEL B RIFKIN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,400,712
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9883023

## Citation

> US National Institutes of Health, RePORTER application 9883023, Altered Mechanotransduction as a Therapeutic Target for Thoracic Aortic Aneurysm (5P01HL134605-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9883023. Licensed CC0.

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