# Pannexin Channels In Vascular Physiology & Inflammation

> **NIH NIH P01** · UNIVERSITY OF VIRGINIA · 2020 · $2,450,733

## Abstract

OVERALL PROJECT SUMMARY
Inter-cellular communication between cells within a tissue environment is fundamentally important for many
physiological processes. Channels and transmembrane transporters that conduct ions and other molecules
across the plasma membrane in healthy living cells are also linked to pathologies of the cardiovascular and
respiratory systems. Extracellular nucleltides (such as ATP) and their derivatives, as well as other metabolites
critically influence many aspects of vasculary physiology such as sympthetic nerve-induced vasoconstriction and
blood pressure regulation, as well disease states such as diet-induced cardiometabolic syndromes. Recent
exciting series of observations suggest that the pannexin proteins form channels on the plasma membrane, and
by permeating ions and/or the release of nucleotides in a very regulated manner, these pannexin channels allow
cells to communicate with other cells. Consistent with this, altered expression of pannexin channels have been
linked to cardovascular and metabolic disorders. Independently, the pannexin channels also play a role in
releasing nucleotides from early stage apoptotic cells that appear critical for communicating with phagocytes,
and with the tissue microenvironment. The central hypothesis tested via this PO1 application is that pannexin
channels sit at a critical interphase between normal homeostasis within the cardiovascular system, and the
disease states leading inflammation, and hypertension. The four projects that comprise this proposal address
the role of pannexin channels as follows. Project 1 (Ravichandran) addresses the role of pannexin channels in
apoptotic cell:phagocyte communication, between dying cells and the neighborhood in regulating anti-
inflammatory signaling, and regulating tissue inflammation; Project 2 (Isakson) addresses how pannexin
channels in vascular smooth muscle cells contribute to vasoconstriction in resistance vessels to regulate blood
pressure, and how Pannexin 1 links sympathetic nervous system to arterial function; Project 3 (Leitinger)
addresses how pannexin channels regulate inflammation and fibrosis of the liver as part of the larger
cardiometabolic syndrome; Project 4 (Bayliss) addresses molecular mechanisms of pannexin channel activation
in physiological and diseased states. With the combination of mouse models and ex vivo studies, and
mechanistic approaches, and identification of new compounds capable of altering Panx1 function, we expect to
provide exciting new insights on pannexin channels and purinergic signaling in vascular physiology and
hypertension, and the basis for novel treatment strategies targeting the regulated opening and closing of these
channels in specific disease states. We expect our studies have a broad impact to cardiovascular, metabolic,
and and respiratory diseases.

## Key facts

- **NIH application ID:** 9894828
- **Project number:** 5P01HL120840-07
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Kodi S Ravichandran
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,450,733
- **Award type:** 5
- **Project period:** 2014-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894828

## Citation

> US National Institutes of Health, RePORTER application 9894828, Pannexin Channels In Vascular Physiology & Inflammation (5P01HL120840-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9894828. Licensed CC0.

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