# Mechanisms of renin angiotensin modulation in thoracic aortic aneurysms

> **NIH NIH F30** · UNIVERSITY OF KENTUCKY · 2021 · $43,460

## Abstract

ABSTRACT
 Thoracic aortic aneurysms (TAAs) are a common, clinically-silent dilatation of the aorta. However,
complications of this disease - such as aortic dissection and rupture - are sudden and deadly. Because there is
currently no validated medical therapy to prevent or reverse aortic dilation, all patients with thoracic aortic
aneurysms will eventually need surgical repair.
 Marfan syndrome is caused by mutations in fibrillin-1, a large extracellular matrix protein responsible for
elastin structure and aortic integrity. Our project proposes the use of Marfan syndrome model mice to
investigate the pathogenesis of TAAs. We have shown that TAAs occur in an angiotensin receptor (AT1a
receptor) dependent manner. How AT1a receptors are activated in Marfan syndrome is a gap in current
knowledge.
 AT1a receptors are canonically activated by its main effector peptide, angiotensin II. It can also be
activated in a ligand independent manner. We hypothesize that AT1a receptors in Marfan syndrome are
activated in an AngII dependent manner. Furthermore, we hypothesize that depletion of endogenous AngII
sufficiently attenuates TAA development in Marfan syndrome through inhibition of AT1a receptor activity.
 To test this hypothesis, we will determine if AngII depletion by angiotensinogen antisense
oligonucleotide administration attenuates aortic dilation, aortic medial remodeling, and aortic AT1a receptor
activity. We will also perform a retrospective clinical study using a large electronic health record dataset to
determine if inhibition of AngII formation, angiotensin receptor blockade, or beta-blockade are associated with
protection against TAA in Marfan syndrome patients.
 Altogether, completion of this project will provide a better understanding of the molecular mechanism
behind Marfan syndrome associated thoracic aortic aneurysm pathogenesis.

## Key facts

- **NIH application ID:** 10242785
- **Project number:** 5F30HL143943-03
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Jeff Zheying Chen
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $43,460
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-05-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242785

## Citation

> US National Institutes of Health, RePORTER application 10242785, Mechanisms of renin angiotensin modulation in thoracic aortic aneurysms (5F30HL143943-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242785. Licensed CC0.

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