# Mechanistic bases of vessel diameter regulation by Plexind1 - Resubmission

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $768,437

## Abstract

PROJECT SUMMARY
 Blood vessels must be properly shaped and placed and have a hierarchical organization with characteristic
and distinct calibers to perform their vital circulatory function. In particular, vascular caliber is the primary
determinant of blood flow properties. Thus, abnormalities in luminal morphometry disrupt blood circulation
and decrease cardiovascular health. We found that Semaphorin-Plexind1 (Sema-Plxnd1) signaling, known for
its role in guiding the anatomical patterning of the vasculature, plays a novel blood flow-dependent role in
determining the caliber of the axial midline vessels (the major artery and vein of the body). Our aims are as
follows. (1) To define the signaling pathways and cellular mechanisms by which Plxnd1, its Sema3 ligands, and
blood flow regulate the caliber of these vessels. (2) To define the structural bases of Plxnd1-dependent vessel
caliber sizing and the role of Semas and flow forces as modulators of Plxnd1 expression, apicobasal targeting,
and flow mechanosensing activity. We will use zebrafish as our primary model system to exploit its unique
experimental advantages for studying vascular development, function, and signaling in vivo. We will also
perform experiments with mice to determine if the receptor's novel role is conserved in mammals. Finally, to
further illuminate how Sema ligands and circulatory forces modulate Plexin-D1 expression, localization, and
function, we will perform studies with human endothelial cell systems under tunable flow conditions.

## Key facts

- **NIH application ID:** 10522665
- **Project number:** 1R01HL161090-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Jesús Torres-Vázquez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $768,437
- **Award type:** 1
- **Project period:** 2022-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522665

## Citation

> US National Institutes of Health, RePORTER application 10522665, Mechanistic bases of vessel diameter regulation by Plexind1 - Resubmission (1R01HL161090-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10522665. Licensed CC0.

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