# Defining the Mechanisms of Lymphatic Vascular Growth and Function

> **NIH NIH R01** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2024 · $529,343

## Abstract

PROJECT SUMMARY/ABSTRACT
Growth of lymphatic vessels from pre-existing vessels is achieved via lymphangiogenesis. The mechanisms that
control lymphangiogenesis remain incompletely understood. VEGF-C binding to, and activation of, its cognate
receptor VEGFR3 is the most well-studied pro-lymphangiogenic pathway known, and is necessary for the
formation, migration and proliferation of lymphatic endothelial cells (LECs). Indeed, humans and mice harboring
dominant negative mutations in VEGFR3 feature hypoplastic lymphatic vessels. In contrast, VEGF-C
overexpression in mice results in lymphatic vessel overgrowth and dysplasia. Hence, a delicate balance of
VEGF-C/VEGFR3 signaling is necessary for the proper patterning of the lymphatic vasculature. We have
identified laminar shear stress (LSS) as an enhancer of VEGF-C signaling. We have also identified the G protein-
coupled receptor (GPCR) sphingosine 1-phosphate (S1P) receptor 1 (S1PR1) as an antagonist of VEGF-C
signaling that is enhanced by LSS. We will dissect the mechanisms by which LSS and S1PR1 regulate VEGF-
C signaling. We will also investigate the significance of this mechanism during health and disease by using
mouse models.

## Key facts

- **NIH application ID:** 10739291
- **Project number:** 5R01HL131652-07
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** Rajanarayanan S Srinivasan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $529,343
- **Award type:** 5
- **Project period:** 2016-06-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10739291

## Citation

> US National Institutes of Health, RePORTER application 10739291, Defining the Mechanisms of Lymphatic Vascular Growth and Function (5R01HL131652-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10739291. Licensed CC0.

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