# FXR1 Regulates Blood Pressure by Altering Contraction of Smooth Muscle

> **NIH NIH F31** · TEMPLE UNIV OF THE COMMONWEALTH · 2022 · $31,586

## Abstract

Abstract
Introduction: Hypertension is a major risk factor for heart disease and stroke. Optimally treated hypertensive
patients still have 50% greater cardiovascular risk than untreated normotensive subjects. Despite current
medication, half a million deaths in the United States include hypertension as a primary contributing cause in
2018 presenting a need for additional targets. Vascular smooth muscle cells (VSMCs) are the fulcrum of vascular
disease, particularly hypertension. VSMCs play an essential role in vascular contractility and the regulation of
blood pressure. Fragile X-related protein (FXR1) is a muscle-enhanced RNA binding protein and we previously
found siRNA knock down of FXR1 increases inflammatory mRNA stability. Overexpression of FXR1 decreases
inflammatory mRNA stability in VSMC. Little is known concerning FXR1 protein binding partners and its role in
vascular disease. The specific aim of this study is to test the hypothesis that FXR1 regulates vascular contractility
by RNA stability and protein interactions.
Results: We generated a novel, VSMC-specific FXR1 conditional knock out mouse (FXR1VSMC/VSMC) in order to
establish an in vivo role of FXR1 in vascular disease. Preliminary data indicates that these mice are hypotensive
as they show decreased systolic (P < 0.001) and diastolic (P < 0.01) blood pressure , and increased resting heart
rate (P < 0.05) at baseline compared to controls. Gene ontology of RNA immuno-precipitation sequencing
analysis in human VSMCs identified that FXR1 binds to mRNA that participate in VSMC contractility and
regulation of blood pressure- related pathways. Although considered an RNA stability protein, mass-
spectrometry identified that FXR1 interacts with proteins related to contractile processes such as cell migration,
adhesion and stress fiber formation. siRNA knock down of FXR1 decreased VSMC migration and collagen gel
contraction corroborating in vivo observations.
Conclusion: These data are the first to suggest FXR1 regulates blood pressure and vascular contractility
potentially by two mechanisms: mRNA stability and functional activity by protein-protein interactions. The findings
support FXR1 activity may represent a target for therapeutic invention to regulate blood pressure.

## Key facts

- **NIH application ID:** 10465895
- **Project number:** 1F31HL160211-01A1
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Amanda St. Paul
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $31,586
- **Award type:** 1
- **Project period:** 2022-07-01 → 2023-06-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465895

## Citation

> US National Institutes of Health, RePORTER application 10465895, FXR1 Regulates Blood Pressure by Altering Contraction of Smooth Muscle (1F31HL160211-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10465895. Licensed CC0.

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