# Eliciting Estrogen's Protective Vascular Effects

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2020 · $376,802

## Abstract

PROJECT SUMMARY
 Menopause increases arterial stiffness which accelerates end organ damage, increases cardiac afterload,
and promotes heart failure with preserved ejection fraction, a disease twice as common in women than men.
Since the Women's Health Initiative reported that postmenopausal estrogen therapy induces adverse vascular
effects, new drugs are needed to protect aging women from cardiovascular disease. We propose that selective
therapies targeting the recently-discovered G protein-coupled estrogen receptor (GPER) will reduce
cardiovascular risk in postmenopausal women.
 Our preliminary data indicate a crucial role for GPER in vascular protection: GPER activation attenuates
salt-induced vascular remodeling while GPER deletion increases pulse pressure, an in vivo indicator of arterial
stiffness. This project will demonstrate that GPER protects the vasculature through a novel molecular
mechanism by which nongenomic estrogen signaling decreases ROS and attenuates glycosaminoglycans
(GAGs) in the extracellular matrix, thereby preserving the mechanical properties of central arteries and
decreasing pulse wave velocity. Moreover, an aging-induced decrease in vascular GPER expression promotes
adverse responses to estrogen but can be corrected with selective therapeutics that target this receptor.
 We propose that vascular GPER protects from arterial stiffness, and targeting this receptor will
improve responses to postmenopausal hormone therapy. Using a combination of in vivo, ex vivo, and in
vitro approaches will allow us to assess our hypothesis in multiple ways. High-frequency ultrasound will allow
in vivo measurement of pulse wave velocity, the gold standard for assessing vascular stiffness. As opposed to
traditional uniaxial pressure myography, biaxial mechanical phenotyping performed in collaboration with a
biomedical engineer will allow the use of computational models to delineate the contributing factors for arterial
stiffness. ROS measurements will be obtained using electron spin resonance spectroscopy, a direct and
sensitive approach for quantifying free radicals in biological samples. Moreover, an inducible, cell-specific
GPER knockout mouse model will allow us to specifically assess the impact of decreased vascular GPER
expression during adulthood on the response to nonselective estrogen therapy.

## Key facts

- **NIH application ID:** 9861025
- **Project number:** 5R01HL133619-04
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Sarah Hoffmann Lindsey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $376,802
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9861025

## Citation

> US National Institutes of Health, RePORTER application 9861025, Eliciting Estrogen's Protective Vascular Effects (5R01HL133619-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9861025. Licensed CC0.

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