# Interplay of Sex Hormones and Chromosomes in Vascular Oxidative Stress and Arterial Stiffening

> **NIH NIH K99** · TULANE UNIVERSITY OF LOUISIANA · 2021 · $85,040

## Abstract

Project Summary
 Sex steroids and chromosomes both contribute to the sexual dimorphism in CVD.
Vascular oxidative stress is one mechanism that is elevated in men compared with women due
to the protective effects of estrogen. While the impact of sex hormones is extensively studied,
sex chromosomes complementation has been overlooked in the context of CVD. Female sex
chromosomes (XX) are associated with worse cardiovascular outcomes during hypertension,
stroke, and pulmonary hypertension. Remarkably, studies on the role of sex chromosomes in
vascular oxidative stress are still lacking. Therefore, we have proposed to elucidate the role of
sex chromosomes in vascular oxidative stress associated with CVD. In the K99 phase, our first
aim will establish that in the absence of sex hormones, XX promotes vascular ROS and arterial
stiffening. This aim will unequivocally determine the impact of sex chromosomes on arterial
stiffness and elucidate the molecular mechanisms. We will use the four core genotype (FCG)
mice which includes females with ovaries and testes and males with testes and ovaries. We will
also use state-of-the-art equipment such as high resolution ultrasound for pulse wave velocity,
biaxial pressure myography for arterial biomechanics, and electron spin spectroscopy for
assessing reactive oxygen species. The second aim will elucidate the molecular mechanisms
by which estrogen preserves X chromosome inactivation to suppress X-linked gene expression
and vascular oxidative stress. We will use fluorescent in situ hybridization to localize X-inactive
specific transcript and map the dynamic structure and localization of the sex chromosomes. Our
overall goal is to determine whether sex hormones and chromosomes interact in CVD and are
associated with vascular oxidative stress. In the future, identifying X-linked genes that contribute
to oxidative stress will provide novel targets for sex-specific therapies to treat or prevent CVD.
In the R00 phase, the third, fourth and fifth aims will determine whether estrogen mediated Xist
RNA localization impacts telomere length, mitochondrial oxidative stress and T-cell mediated
vascular damage. The MOSAIC K99/R00 award will enable my training and career development
in novel techniques that will allow separation from my mentor and transition to independency.
Moreover, this proposal will not only progress scientific research in CVD, but advance the
training and fellowship of future minority scientists in biomedical sciences

## Key facts

- **NIH application ID:** 10106296
- **Project number:** 1K99HL155841-01
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Benard Ojwang Ogola
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $85,040
- **Award type:** 1
- **Project period:** 2021-01-18 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10106296

## Citation

> US National Institutes of Health, RePORTER application 10106296, Interplay of Sex Hormones and Chromosomes in Vascular Oxidative Stress and Arterial Stiffening (1K99HL155841-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10106296. Licensed CC0.

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