# Vascular cell sexual dimorphism in complex mechanical microenvironments

> **NIH NIH F31** · UNIVERSITY OF FLORIDA · 2020 · $29,701

## Abstract

The sex disparity in the incidence and progression of cardiovascular disease (CVD), including peripheral arterial
disease (PAD), is a troubling clinical observation. It is well known that CVD manifests differently in men and
women, with more women than men suffering from the disease. Further, within the vascular network, there are
mechanical microenvironments that favor CVD development, for example, atherosclerotic plaques preferentially
form at regions of disturbed flow and low fluid shear stresses such as, vasculature bifurcations. Yet, no reports
have correlated these two separate observations at the cellular level, specifically, the sex differences in
CVD and local vascular mechanics. This project aims to 1) assess the functional changes in male and female
human umbilical vein endothelial cells in response to combined physiological fluid shear stresses and
substrate stiffness by morphometric, secretory, and genetic analyses, 2) assess the functional changes in
male and female human aortic smooth muscle cells in response to combined physiological cyclic stretching
and substrate stiffness by morphometric, mechanical, and genetic analyses, and 3) correlate the disparate
functional response of male and female vascular cells using statistical methods. Upon completion of these
aims, a foundational understanding of vascular cell functionality in vitro as it pertains to sexual dimorphism in
complex mechanical microenvironments will be gained. A factorial design of experiments will be used to
systematically assess the influence of cell sex, laminar fluid shear stress or cyclic stretch, and the underlying
substrate stiffness. The effects of the mechanical microenvironment will be assessed using well-defined flow and
stretch bioreactors with RGD-conjugated polyacrylamide gel substrates. Cell morphology will be quantified by
immunofluorescence microscopy methods. Glycocalyx, vasoregulatory, and estradiol secretory products will be
quantified by commercial assays. Cellular mechanical properties will be measured by atomic force microscopy.
The regulation of a large set of vascular cell genes including a subset related to CVD will be measured by
quantitative reverse transcription polymerase chain reaction. Statistical analyses will be performed to relate gene
expression results to morphological, secretory, and mechanical responses and then to correlate them to a given
sex and mechanical force combination. This work follows the 2015 NIH mandate to consider sex as a biological
variable by investigating the clinical observations of the sex disparity in cardiovascular disease at the cellular
level. The significance for this work is that future imaging modalities that quantify vascular forces such as with
4D MRI, will be able to indicate areas within the vasculature that are susceptible to localized cellular dysfunction
using correlative statistical models and ultimately predict a patient's location-specific vulnerability for disease.
This proposal is part of a ...

## Key facts

- **NIH application ID:** 10026024
- **Project number:** 5F31HL147445-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Bryan Daniel James
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $29,701
- **Award type:** 5
- **Project period:** 2019-09-16 → 2021-05-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10026024

## Citation

> US National Institutes of Health, RePORTER application 10026024, Vascular cell sexual dimorphism in complex mechanical microenvironments (5F31HL147445-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10026024. Licensed CC0.

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