# Effects of Sex on the Elastogenesis of Vascular Elastic Fibers

> **NIH NIH P20** · UNIVERSITY OF NEBRASKA OMAHA · 2024 · $252,749

## Abstract

PROJECT SUMMARY – Effects of Sex on the Elastogenesis of Vascular Elastic Fibers
Elastic fibers and laminae are responsible for compliance and elastic recoil in many tissues, including arteries.
The production of mature elastic structures occurs during late fetal and early neonatal periods and is thought to
cease in adulthood. Though these structures are mechanically and chemically stable, long human lifespans
subject elastin to cyclic mechanical stress and proteolytic destruction that increase arterial stiffness and lead to
a myriad of cardiovascular events, including hypertension, cardiomyopathy, kidney disease, and peripheral
arterial disease, that are often delayed in women compared to men. Elastin regeneration could help avoid arterial
stiffening but has not been described in adult human tissues. Our recent analysis demonstrates that elastic fibers
in the external elastic lamina (EEL) of human femoropopliteal arteries (FPAs) often contain long breaks filled by
thinner continuous fibers that have a different pitch than the rest of the EEL. These breaks are present in both
young healthy arteries with no vascular pathology or inflammation, and in old diseased arteries. Elastic fibers
filling these breaks are autofluorescent, and stain positive for Verhoeff-Van Gieson and periodic acid-Schiff
stains, indicating the presence of an elastin core and a higher proportion of microfibrillar structure typical of a
newly synthesized fiber. In combination with animal model findings suggesting that pregnancy incites a burst in
elastic fiber synthesis in the vaginal tissue, these data allow hypothesizing that the production of continuous
vascular elastic fibers occurs in maturity and that the female sex has a positive effect on this process,
which may partially explain the sex-related vascular health disparities. To test this hypothesis, we will first
determine whether the elastic fibers filling EEL breaks in healthy arteries are newly synthesized or are
undergoing degradation using human FPAs from tissue donors and performing biaxial mechanical
characterization, constitutive modeling, multiphoton microscopy, histological/immunohistochemical analyses,
and mass spectrometry to compare the biomechanics, microstructure, and molecular characteristics of segments
with and without the breaks. Second, we will determine if women have a greater proportion of filled EEL breaks
than men using an existing histological biobank from >1,000 human FPAs available in the Tissue Analysis Core
(TAC). Statistical modeling and machine learning will help determine ethnic and risk factors contributing to filled
EEL breaks in women and men of different ages. This project will leverage the unique resource of human arteries
and TAC’s expertise to challenge the existing paradigm that the production of continuous elastic fibers does not
occur in maturity. It will determine if the elastin modification process is different in women than in men, which
could help explain the frequently del...

## Key facts

- **NIH application ID:** 10770979
- **Project number:** 1P20GM152301-01
- **Recipient organization:** UNIVERSITY OF NEBRASKA OMAHA
- **Principal Investigator:** Majid Jadidi
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $252,749
- **Award type:** 1
- **Project period:** 2024-02-15 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10770979

## Citation

> US National Institutes of Health, RePORTER application 10770979, Effects of Sex on the Elastogenesis of Vascular Elastic Fibers (1P20GM152301-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10770979. Licensed CC0.

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