# Identifying the role of aortic valve interstitial cells and altered micro-environment on bicuspid aortic valve disease progression.

> **NIH NIH F31** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $36,936

## Abstract

PROJECT SUMMARY/ABSTRACT
The bicuspid aortic valve (BAV) is the most common cardiac congenital defect and contains two, as opposed to
the normal three, leaflet tissues. BAVs commonly become diseased at a faster rate than structurally normal aortic
valves (AVs) most often due to calcium build up which eventually leads to aortic stenosis (AS). Current clinical
treatments for AS in BAV patients consist only of surgical options such as AV repair and replacement, with
replacement being the more common. Bioprosthetic valves are routinely used in replacement scenarios despite
their limited lifespan of 10-15 years. In the context of BAV patients, who tend to disease at earlier time points in
life, bioprosthetic valves are not an indefinite solution and will most likely require follow-up surgical operations.
Alternatively, mechanical valves are employed for the younger BAV patient population but require the indefinite
need for anticoagulants which substantially hinders patient quality of life. Thus, no optimal nor indefinite surgical
intervention currently exists to treat BAV disease. Previous work from our lab and others have elucidated drastic
differences in extracellular matrix (ECM) composition and structure as well as differences in the mechanical
stress-strain environment between AVs and BAVs. However, it has yet to be elucidated as to how these changes
affect BAV interstitial cell (BAVIC) functional remodeling behaviors. In addition, limited work has been done to
explore whether BAV disease may be caused by intrinsic differences between the BAVICs and normal AV
interstitial cells (AVICs). We hypothesize that the intrinsic differences of BAVICs, the altered microenvironment,
and the altered BAV leaflet strains enhance BAV disease progression through cell-mediated ECM remodeling
and biosynthesis brought on by phenotypic activation of the BAVIC population. We will address this hypothesis
with the following three aims:
Identifying the 3D morphological and ECM regional variations within the BAV. We will utilize state-of-the-
art methods including 3D small angle light scattering, quantitative histology, and focused-ion beam scanning
electron microscopy to assess the differences in ECM between the BAV and AV.
Delineating the biophysical state and biosynthetic behaviors of isolated BAVICs and AVICs within
peptide-modified poly (ethylene glycol) (PEG) hydrogels of varying stiffness. We will assess the contractile
and biosynthetic properties of isolated BAVICs and AVICs within PEG hydrogels to investigate intrinsic
differences among the cell groups.
Emulating BAV leaflet strains to assess BAVIC remodeling behaviors in vitro. Here we will use a uniaxial
stretch bioreactor to emulate BAV strain levels and assess how altered kinematics affect BAVIC responses.

## Key facts

- **NIH application ID:** 10364606
- **Project number:** 5F31HL154654-02
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Alex Khang
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $36,936
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364606

## Citation

> US National Institutes of Health, RePORTER application 10364606, Identifying the role of aortic valve interstitial cells and altered micro-environment on bicuspid aortic valve disease progression. (5F31HL154654-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10364606. Licensed CC0.

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