# MiR-204 regulates type 1 IP3R/Ca2+ axis to control vascular smooth muscle cell contractility and blood pressure: Potential role of the gut microbiome

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2022 · $469,271

## Abstract

Project Summary
Hypertension is a multi-system disease. Commensal bacteria that inhabit the gut (gut
microbiome) can affect vascular tone and modulate blood pressure. Normotensive animals
become hypertensive when transplanted with gut microbiota from hypertensive animals, and
vice versa. Furthermore, hypertension in humans is associated with specific alterations in gut
microbial diversity, lending credence to the premise that a change in gut microbial load and
diversity (dysbiosis) contributes to the pathogenesis of hypertension.
This application lies at the intersection of gut dysbiosis and hypertension. It posits that gut
dysbiosis is a key driver of increased vascular tone in hypertension It also puts forth the
hypothesis that vascular smooth muscle-enriched microRNA-204 (miR-204) relays metabolic
signals originating from gut bacteria to control smooth muscle contraction via its effects on
sarcoplasmic reticulum Ca2+ release into the cytoplasm.
The application is supported by strong preliminary data. It shows a change in the gut microbial
community, and microbe-derived metabolites, in hypertensive mice. It further shows that
antibiotic-induced gut dysbiosis in mice downregulates vascular smooth muscle miR-204, leads
to hypercontractility of blood vessels, is associated with upregulation of Inositol 1,4,5-
trisphosphate (IP3) receptor (IP3R1) which controls vascular smooth muscle cytosolic Ca2+, and
deregulates vascular smooth muscle intracellular Ca2+ homeostasis.
This application is highly novel, mechanistic as well as potentially translatable. It will leverage
unique tissue-targeted genetically modified mice, and in vitro tools, to dissect the relationship
between miR-204, the gut microbiome, and the sarcoplasmic reticulum Ca2+ apparatus in
vascular smooth muscle cells. In addition, it will use state-of-the-art methodologies to assess
Ca2+ flux in cells and in vessels of live animals. Finally, it will explore whether bacterial
metabolites can reverse deregulation of Ca2+ homeostasis and mitigate the development of
hypertension.
Given the enormous interest in how the human microbiome impacts health and disease, this
application provides a unique opportunity to explore how a microRNA regulated by gut bacteria
modulates blood pressure. Such information will open the door for microRNA-based and/or
microbiota-based therapeutics to prevent or treat hypertension.

## Key facts

- **NIH application ID:** 10447756
- **Project number:** 5R01HL150360-04
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Modar O. Kassan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $469,271
- **Award type:** 5
- **Project period:** 2020-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447756

## Citation

> US National Institutes of Health, RePORTER application 10447756, MiR-204 regulates type 1 IP3R/Ca2+ axis to control vascular smooth muscle cell contractility and blood pressure: Potential role of the gut microbiome (5R01HL150360-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10447756. Licensed CC0.

---

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