# Determinants of Aorta Heterogeneity

> **NIH NIH R35** · UNIVERSITY OF KENTUCKY · 2021 · $596,149

## Abstract

Abstract
Aortopathies, including aneurysms, dissection, and rupture, represent a key challenge in HLBS
research. In the past twenty years of our continuously funded research on aortopathies, we
have contributed to many mechanistic insights into the aortopathy research including a new
concept: There are regional characteristics of the aorta in regard to diverse embryonic origins
and functions of cells. The overall hypothesis of this R35 program is that heterogeneity of
cellular origins imparts functional variances along the length of the aorta, including diversity of
extracellular matrix stability, which in turn contributes to regional specificity of aortopathies.
Regional specificity of aortopathies is present in many mouse models that we have validated
and characterized. Our initial single cell transcriptomic and proteomic data have also implicated
new potential contributors to heterogeneity of the normal aortic biology and aortopathies. Three
major themes are proposed in this program: (1) What are the structural and molecular
mechanisms that contribute to biological and pathophysiological heterogeneity along the length
of the aorta? (2) Are cellular and extracellular heterogeneity a basis for regional specificity of
aortopathies? (3) How do signaling pathways, extracellular matrix, and crosstalk between
resident aortic cells coordinate to promote the heterogeneity of aortopathies? We have robust
tools including a spectrum of reagents, multiple classic and new mouse models,
ultrasonography, MRI, intravital microscopy, proteomics, and single cell RNA sequencing
techniques. In addition to aortopathy research, the PI has more than 30-year expertise in the
fields of lipoprotein metabolism, inflammation, and atherosclerosis research. Aortopathies are
not a sole aortic disease, but is associated with a wide range of diseases or syndromes that
may affect skin, lung, kidney, brain, bone, and other organs. The proposed research program
will benefit from the flexibility to pursue potential contributions of other tissues and organs to
aortopathies, and vice versa the influences of aortopathies on other tissues and organs. This
R35 mechanism will also benefit the PI’s strength in basic research, enhance his interaction with
the translational research in the clinical arena, and train the next generation of scientists.

## Key facts

- **NIH application ID:** 10108115
- **Project number:** 1R35HL155649-01
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Alan Daugherty
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $596,149
- **Award type:** 1
- **Project period:** 2021-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10108115

## Citation

> US National Institutes of Health, RePORTER application 10108115, Determinants of Aorta Heterogeneity (1R35HL155649-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10108115. Licensed CC0.

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