# Vascular Smooth Muscle Function in Pulmonary Hypertension

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2021 · $378,750

## Abstract

PROJECT SUMMARY/ABSTRACT
Pulmonary hypertension (pHTN) is a complex, progressive condition leading to increased pulmonary vascular
resistance, right heart failure and ultimately death. Although pHTN arises from a variety of genetic and
pathogenic causes, it is widely recognized that structural alterations in the vascular wall contribute to all forms
of pHTN. A chronic shift in cellular metabolism from mitochondrial oxidative phosphorylation to aerobic
glycolysis underlies the hyperproliferative and anti-apoptotic phenotype within the pulmonary vasculature.
These metabolic derangements are accompanied by H+ extrusion creating an alkalotic intracellular pH while
acidifying the extracellular microenvironment; conditions that activate the H+-gated acid sensing ion channel 1
(ASIC1). ASIC1 conducts both Na+ and Ca2+ and activation leads to membrane depolarization and variety of
intracellular Ca2+ signaling events. Our previous studies show ASIC1 contributes to the development of pHTN
and is associated with greater localization of ASIC1 at the plasma membrane of pulmonary arterial smooth
muscle cells (PASMC) and loss of ASIC1 in the mitochondria. Neither the role of ASIC1 in the mitochondria, nor
the contribution of ASIC1 to metabolic-mitochondrial dysfunction are known. Therefore, the overall objective
of this application is to determine the contribution of ASIC1 to the metabolic derangements that promote a
proliferative, apoptosis-resistant phenotype associated with pHTN. We will test the central hypothesis that
ASIC1 contributes to metabolic dysfunction in pHTN as a result of altered subcellular localization and
regulation of PASMC plasma membrane and mitochondrial membrane potential with the following two
specific aims: 1) Determine the impact of altered cellular metabolism on ASIC1 localization and activation.
We will test the working hypothesis that enhanced glucose uptake and subsequent acidification of the
extracellular microenvironment in pHTN leads to increased localization/activation of ASIC1 at the plasma
membrane, plasma membrane depolarization, and proliferation. 2) Examine the functional role of
mitochondrial ASIC1 (mtASIC1) in regulation of mitochondrial membrane potential (m) and apoptosis.
We will test the working hypothesis that mtASIC1 contributes to mitochondrial m depolarization and
apoptosis. Furthermore, loss of mtASIC1 in pHTN leads to mitochondrial m hyperpolarization and
apoptosis-resistance. Successful completion of the proposed studies is expected to define a role for ASIC1 in
regulating mitochondrial dynamics and metabolic dysfunction. These outcomes will enable a fundamental
understanding of ASIC1 in various proliferative and degenerative diseases, which will permit future studies to
evaluate the therapeutic potential of ASIC1.

## Key facts

- **NIH application ID:** 10166899
- **Project number:** 5R01HL111084-08
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Nikki L Jernigan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $378,750
- **Award type:** 5
- **Project period:** 2013-02-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166899

## Citation

> US National Institutes of Health, RePORTER application 10166899, Vascular Smooth Muscle Function in Pulmonary Hypertension (5R01HL111084-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10166899. Licensed CC0.

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