# Influences of sex hormones on the microtubule cytoskeleton in right ventricular dysfunction

> **NIH NIH F32** · UNIVERSITY OF MINNESOTA · 2021 · $72,630

## Abstract

Project Summary
The goals of this proposal are to further train Sasha Prisco, MD, PhD as a physician-scientist in Cardiology and
to advance the understanding of the mechanisms of right ventricular dysfunction in pulmonary hypertension.
Pulmonary arterial hypertension is caused by pathological remodeling of the pulmonary vasculature which
subsequently increases right ventricular afterload, leading to right ventricular failure. Unfortunately, there are
no current therapies that directly target the right ventricle. Despite the fact that females outnumber males by 3-
4:1 in pulmonary arterial hypertension, males develop more severe right ventricular dysfunction and
subsequently die sooner. We have previously shown that the microtubule-junctophilin-2 (MT-JPH2) pathway is
dysregulated in a preclinical model of pulmonary arterial hypertension. While there are data linking sex
hormones to microtubules, a clear mechanism by which sex hormones regulate microtubules has not been
established. This research project will investigate the role of sex hormones on the microtubule cytoskeleton
and right ventricular function in pulmonary arterial hypertension. Aim 1 tests the hypothesis that estrogen has
anti-microtubule properties, which augment right ventricular function by limiting microtubule-dependent
junctophilin-2 dysregulation (MT-JPH2 pathway) and t-tubule remodeling in preclinical right ventricular
overload. Aim 2 examines the hypothesis that testosterone stabilizes microtubules, which exerts a negative
effect on right ventricular function by promoting microtubule-mediated junctophilin-2 downregulation and t-
tubule remodeling in experimental models of right ventricular pressure overload. In both aims, we will evaluate
how the sex hormones, estrogen and testosterone, affect microtubule polymerization and microtubule stability
and whether sex hormones directly interact with microtubules with advanced microscopy. Furthermore, we will
investigate how estrogen and testosterone regulate expression of the MT-JPH2 pathway in isolated right
ventricular cardiomyocytes. Finally, we will assess how alterations of estrogen and testosterone affect the MT-
JPH2 pathway and right ventricular function in two rat models of right ventricular pressure overload
(monocrotaline and pulmonary artery banded), right ventricle pressure overloaded rats that have either
undergone oophorectomy or castration, and oophorectomized/castrated right ventricle pressure overloaded
rats given estrogen or testosterone replacement, respectively. This project has potential to provide molecular
mechanistic insight into the divergent response of the right ventricle in pulmonary arterial hypertension based
on sex. The training of Dr. Prisco as a physician-scientist will advance the mission of the NIH by helping
support the training of a scientist who will conduct clinically relevant research.

## Key facts

- **NIH application ID:** 10233015
- **Project number:** 1F32HL154533-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Sasha Zheng Prisco
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $72,630
- **Award type:** 1
- **Project period:** 2021-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233015

## Citation

> US National Institutes of Health, RePORTER application 10233015, Influences of sex hormones on the microtubule cytoskeleton in right ventricular dysfunction (1F32HL154533-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10233015. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*