# Targeting the Caveolae-Dependent Mechanism of Calcifying Extracellular Vesicle Formation

> **NIH NIH R01** · FLORIDA INTERNATIONAL UNIVERSITY · 2023 · $359,560

## Abstract

PROJECT SUMMARY
Vascular calcification is the most significant predictor of cardiovascular morbidity and is especially prevalent in
individuals with chronic kidney disease. Widespread arterial mineral in these patients disrupts vascular function
and increases afterload on the heart. No therapeutic strategies currently exist to prevent or treat vascular
calcification. Development of therapeutics is hindered by an incomplete understanding of the mineral formation
process. Calcific mineral formation in the vascular wall begins in extracellular vesicles (EVs) that promote
interactions between calcium and phosphate ions. Published data show that calcifying EV formation requires the
presence of caveolin-1, a structural component of plasma membrane invaginations known as caveolae.
However, the mechanisms through which caveolae may initiate calcifying EV formation remain unclear. The
proposed study seeks to track the formation of calcifying EVs back to caveolae within vascular smooth muscle
cells. We hypothesize that caveolae trafficking into the cell initiates calcifying EV formation and confers
mineralization potential to the nascent vesicles. We will study the role of epidermal growth factor receptor (EGFR)
as a caveolin-1 interactor and potential novel mediator of calcifying EV formation. Aim 1 of the study explores
the caveolae-dependent mechanisms through which EVs form and promote mineralization. We will analyze the
evolution of calcifying EVs as mineralization progresses both in vivo and in vitro. Aim 2 will test the therapeutic
potential of a clinically-relevant strategy to alter caveolae trafficking and calcifying EV formation to treat vascular
calcification.

## Key facts

- **NIH application ID:** 10532223
- **Project number:** 5R01HL160740-02
- **Recipient organization:** FLORIDA INTERNATIONAL UNIVERSITY
- **Principal Investigator:** Joshua D Hutcheson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $359,560
- **Award type:** 5
- **Project period:** 2021-12-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10532223

## Citation

> US National Institutes of Health, RePORTER application 10532223, Targeting the Caveolae-Dependent Mechanism of Calcifying Extracellular Vesicle Formation (5R01HL160740-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10532223. Licensed CC0.

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