# Anatomic microniches and their contribution to vascular remodeling in pulmonary hypertension

> **NIH VA I01** · MICHAEL E DEBAKEY VA MEDICAL CENTER · 2024 · —

## Abstract

Pulmonary hypertension (PH) is a poorly understood disease that causes pathologic remodeling of the
smaller diameter vessels of the lung, leading to progressive heart failure. This proposal will support the
critically needed studies to advance our currently limited understanding of the development of pulmonary
hypertension. Launching from her career development award findings, the PI (Lavannya Pandit, MD) outlines
a five-year plan to investigate the mechanism by which the K2P (two-pore domain) family of potassium ion
channels attributed to vascular smooth muscle cells participates in the vascular remodeling targeted to the
smaller diameter resistance-vessels of the lung, a defining pathologic characteristic of pulmonary hypertension.
This work will be performed at the Michael E. DeBakey Veterans Affairs medical center (MEDVAMC), which is
affiliated with Baylor College of Medicine in the Texas Medical Center, Houston. Important collaborative studies
will be performed within neighboring institutions at the Texas Medical Center (University of Texas Health
Science Center and University of Houston.) The project has been developed with consultative guidance from
renowned experts in the field of ion channel and pulmonary vascular cell biology who will continue their active
participation over the five-year duration of the proposed studies. Preliminary microarray data from explanted
human PH pulmonary arteries implicated a role for K2P channel dysfunction. We hypothesize that the K2P ion
channel dysfunction causes pathologic growth and constriction of smooth muscle cells specific to the smaller
diameter resistance vessels. The scientific approach utilizes primary pulmonary vascular smooth muscle cells
from both larger conduit and smaller resistance pulmonary vessels of both nonsmoking cadaveric controls and
explanted PH human lung tissues with parallel studies utilizing a mouse model of PH. We will test how
anatomic location determines specific K2P ion channels’ effect on the pulmonary vascular smooth cell
intracellular pathways for growth and contractility. The first objective of this proposal examines how anatomic
location within the pulmonary vascular bed affects K2P ion channel expression and function in vascular smooth
muscles. We will measure K2P channel expression, current density and resting membrane potential in
pulmonary vascular smooth muscle cells, attributing changes in K2P ion channel expression and function to
anatomic origin. The second objective of this proposal maps the interaction between the K2P channel and
endothelin-1(ETR) and thromboxaneA2 receptors (TXA2) by measuring intracellular ETR and TXA2 trafficking
using a radioligand assay and confocal microscopic imaging. These results link anatomic location of the K2P
channels to smooth muscle cell receptor ligand signaling (vasoconstrictors: endothelin-1 and thromboxaneA2)
that are currently implicated in PH. The third objective is to establish a functional role of K2P ion channels in
t...

## Key facts

- **NIH application ID:** 10726569
- **Project number:** 5I01BX004954-03
- **Recipient organization:** MICHAEL E DEBAKEY VA MEDICAL CENTER
- **Principal Investigator:** LAVANNYA M. PANDIT
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-10-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10726569

## Citation

> US National Institutes of Health, RePORTER application 10726569, Anatomic microniches and their contribution to vascular remodeling in pulmonary hypertension (5I01BX004954-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10726569. Licensed CC0.

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