# Ectonucleotidase modulation of age-dependent vascular calcification and stiffness

> **NIH NIH K76** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $243,000

## Abstract

Abstract
With increasing age, blood vessels become stiffer and more calcified. In the latter years of the human lifespan,
the process of vascular aging accelerates. The reason that blood vessels lose their youthful elasticity and
ability to retard the deposition of calcium precipitously later in life is poorly understood. Ectonucleotidases are
found on the surface of endothelial cells which line the inner surface of blood vessels, vascular smooth muscle
cells, and leukocytes. The ectonucleotidase CD39 is responsible for cleaving ATP and ADP to form AMP, and
subsequently, CD73 is responsible for generating adenosine from AMP. Since ATP and ADP are pro-
inflammatory and act in a paracrine fashion, I hypothesize that ectonucleotidase activity plays a role in the
vascular stiffness and calcification that occurs as a consequence of age. This is supported by my preliminary
data in wild type (C57BL/6) mice, which demonstrates CD73 protein levels declined with age (up to 24 months)
in the heart and kidney. This is also supported by preliminary data in mice and human tissues demonstrating
that loss of CD73 expression promoted expression of the transcription factor Runx2, which is critical for
osteogenesis. We hypothesize that loss of ectonucleotidase expression with age could have deleterious
consequences on the vessel wall, resulting in an environment which promotes vascular calcification and
stiffness. Since the role of ectonucleotidases in vascular aging is unknown, we will elucidate mechanisms
which mediate age-dependent vascular calcification through the following aims. Aim 1: We will determine how
age-dependent decline in vascular ectonucleotidase expression renders vessels susceptible to vascular
calcification and fibrosis in a murine model. Aim 2: We will determine how ectonucleotidase activity mitigates
arterial fibrosis and stiffness. Aim 3: We will determine if ectonucleotidase expression plays a role in age-driven
human coronary artery calcification. Achievement of these aims will elucidate the role of ectonucleotidases in
age-dependent vascular calcification and stiffness in mice and humans. The mechanistic insights obtained
from these experiments will define my future investigative direction and serve as a foundation for a subsequent
RO1 application as an independent investigator studying vascular biology and aging.

## Key facts

- **NIH application ID:** 10848477
- **Project number:** 5K76AG064426-05
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Nadia Razaq Sutton
- **Activity code:** K76 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $243,000
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848477

## Citation

> US National Institutes of Health, RePORTER application 10848477, Ectonucleotidase modulation of age-dependent vascular calcification and stiffness (5K76AG064426-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10848477. Licensed CC0.

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