# Evaluation of aortic stiffening as an early indicator of anthracycline-induced cardiotoxicity

> **NIH NIH R21** · NORTHEASTERN UNIVERSITY · 2020 · $189,525

## Abstract

PROJECT SUMMARY
Anthracyclines are common antineoplastic agents of known cardiotoxicity. While early detection and improved
therapeutic approaches have increased the odds of survival for cancer patients, adverse cardiovascular effects
in cancer survivors are often discovered upon occurrence of clinical symptoms, when myocardial injury cannot
be reversed. Given the increasing population of cancer survivors, there is an urgent need to identify a set of
reliable metrics that can estimate the cardiovascular risk in patients treated with anthracyclines. Motivated by
reports of aortic stiffening following anthracycline treatment, and recalling that aortic stiffening is an
independent risk factor for cardiovascular disease, this proposal intends to evaluate the use of aortic stiffness
as an early predictor of cardiovascular dysfunction following anthracycline chemotherapy. To address this
question, our team brings together expertise in cardiac magnetic resonance (MR) imaging, experimental and
computational vascular mechanics, and clinical cardio-oncology. Research activities will focus on a mouse
model of anthracycline-induced cardiotoxicity, a first necessary step to identify temporal correlations between
physiological events that can support and motivate future clinical studies on patient cohorts. In Aim 1, we will
relate the onset of cardiac injury with the progression of cardiac dysfunction and the evolution of aortic
stiffness. Circulating levels of cardiac troponin I will be measured as a biomarker for myocardial damage, MR
imaging of the left ventricular cavity combined with invasive central pressure measurements will be used to
evaluate cardiac function from pressure/volume loops, and in vitro biaxial tests will be performed on isolated
aortic specimens to estimate material, structural, and active stiffness. In Aim 2, progressive changes in stiffness
will be related to the microstructural reorganization of the wall. Combining diverse biological assays (histology,
immunohistochemistry, western blotting), we will quantify deposition and removal of collagen, cell migration,
proliferation, and apoptosis, as well as the timeline for the inflammatory response that is expected to follow the
production of reactive oxygen species associated with anthracycline treatment. Experimental data will inform
a computational model for the growth and remodeling of the aorta that will identify the microstructural
mechanisms responsible for aortic stiffening. Computational results will set the stage for mechanicistic studies
designed to uncover the molecular pathways leading to the predicted microstructural reorganization.

## Key facts

- **NIH application ID:** 9994004
- **Project number:** 5R21HL148747-02
- **Recipient organization:** NORTHEASTERN UNIVERSITY
- **Principal Investigator:** Chiara Bellini
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $189,525
- **Award type:** 5
- **Project period:** 2019-08-10 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994004

## Citation

> US National Institutes of Health, RePORTER application 9994004, Evaluation of aortic stiffening as an early indicator of anthracycline-induced cardiotoxicity (5R21HL148747-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9994004. Licensed CC0.

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