# Probing sex differences in myocardial fibrosis at multiple length scales using biomaterials

> **NIH NIH DP2** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $1,422,000

## Abstract

PROJECT SUMMARY
My proposed research for the NIH Director’s New Innovator Award seeks to determine how biological
sex modulates myocardial fibrosis and develop innovative models of sex-specific tissue remodeling
using advanced biomaterial technologies. Myocardial fibrosis, or the aberrant remodeling of extracellular
matrix in the heart, is a common outcome of several cardiac pathologies, including ventricular pressure overload,
myocardial infarct, hypertension, cardiac inflammation, and/or genetic cardiomyopathies, all of which can lead
to heart failure. Even though standard-of-care medications have been useful to help relieve heart failure
symptoms, clinically effective therapeutics to halt and reverse myocardial fibrosis progression are not available.
Biological sex is a potent modulator of myocardial fibrosis. For example, clinical studies have established that
patients experiencing diastolic dysfunction and develop heart failure with preserved ejection fraction (HFpEF)
are 2.84-fold more likely to be female. Unfortunately, the historical dependence on male-biased disease models
for understanding myocardial fibrosis has left a significant gap in understanding female-specific heart failure
mechanisms, causing significant health disparities in treatment outcomes for female patients. To change
course, our laboratory will develop sex-specific cardiac fibrosis models and determine paths toward
sex-specific therapies to halt disease progression and move toward equitable treatment outcomes. My
proposal outlines an innovative research program to identify how X-chromosome dosage in cardiac
myofibroblasts gives rise to sex differences in myocardial fibrosis after injury. Our three project thrusts centralize
around the hypothesis that X-chromosome dosage regulates (1) myofibroblast activation signaling networks in
cardiac fibroblasts, (2) extracellular matrix remodeling after myocardial injury, and (3) inflammation during
myocardial fibrosis in females. Understanding sex-specific mechanisms of myocardial fibrosis may inform paths
toward sex-specific treatment protocols and significantly impact clinical practice. If successful, the proposed
research will significantly and broadly advance our fundamental understanding of sex-specific biology in
myocardial fibrosis and other cardiovascular diseases.

## Key facts

- **NIH application ID:** 10687446
- **Project number:** 1DP2HL173948-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Brian Alberto Aguado
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,422,000
- **Award type:** 1
- **Project period:** 2023-09-05 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10687446

## Citation

> US National Institutes of Health, RePORTER application 10687446, Probing sex differences in myocardial fibrosis at multiple length scales using biomaterials (1DP2HL173948-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10687446. Licensed CC0.

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