# PKD proteins in endothelial cells

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2021 · $602,338

## Abstract

Project Summary
Endothelial cells line the wall of all blood vessels and regulate a wide variety of functions, including contractility
which controls systemic blood pressure. Dysfunctional endothelial cells are a hallmark of several
cardiovascular diseases, but pathological mechanisms involved are poorly understood. Endothelial cells
express both PKD1 (polycystin-1), an eleven transmembrane domain protein, and PKD2 (polycystin-2), a
transient receptor potential (TRP) channel. Regulatory mechanisms, physiological functions and pathological
involvement during hypertension of PKD1 protein and PKD2 channels in endothelial cells are unclear. Using a
wide variety of approaches and inducible, endothelial cell-specific knockout mice, we provide evidence that
physical coupling of PKD1 to PKD2 in endothelial cells stimulates vasodilation. Preliminary data also suggest
that PKD1/PKD2 channel signaling is dysfunctional during hypertension, which attenuates this vasodilatory
signaling mechanism. In this proposal, we will investigate three specific aims. Aim 1 will test the hypothesis
that endothelial-dependent physiological stimuli activate PKD1/PKD2 coupling in endothelial cells, leading to
vasodilation. Aim 2 will investigate the mechanisms by which endothelial-dependent stimuli activate
PKD1/PKD2 channels in endothelial cells to produce vasodilation. Aim 3 will study the hypothesis that
hypertension is associated with pathological alterations in PKD1/PKD2 channel signaling in endothelial cells
that inhibits vasodilation mediated by these proteins. Methods used will include RT-PCR, Western blotting,
biotinylation, FRET, RNAi, co-IP, immunofluorescence, patch-clamp electrophysiology, membrane potential
recording, intracellular Ca2+ imaging, arterial myography and blood pressure telemetry. This project will
provide significant novel information concerning vasoregulation by endothelial cell PKD1 and PKD2 proteins.

## Key facts

- **NIH application ID:** 10097912
- **Project number:** 1R01HL155180-01
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Jonathan H Jaggar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $602,338
- **Award type:** 1
- **Project period:** 2021-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10097912

## Citation

> US National Institutes of Health, RePORTER application 10097912, PKD proteins in endothelial cells (1R01HL155180-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10097912. Licensed CC0.

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