# TRPC4-mediated calcium signals accelerate vascular remodeling in pulmonary arterial hypertension

> **NIH NIH K25** · UNIVERSITY OF SOUTH ALABAMA · 2021 · $159,548

## Abstract

Abstract
 Pulmonary arterial hypertension (PAH) is an incurable disease of elevated pulmonary artery pressure that
culminates in death due to right heart failure. The etiology of PAH is comprised of increased vasoconstriction in
resistance arteries and remodeling of the arterial microcirculation. All current therapies for PAH target
vasoconstriction, but patient survival has not improved because remodeling remains irreversible. Thus, there
has been considerable impetus to determine the mediators of remodeling in PAH. Members of the transient
receptor potential (TRP) family ion channels have been implicated as drivers of vascular proliferation and
remodeling in PAH. Our lab has shown that TRPC4, a subtype of the canonical TRP family, increases
mortality and vascular lesion number and severity in PAH. A separate mechanism of hemodynamic
perturbations resulting in turbulent or oscillatory endothelial shear stress has also been associated with
increased vascular resistance and remodeling in PAH. Given that both TRPC4 and shear-induced signals
are linked by the nexus of intracellular calcium, we hypothesize that TRPC4 and shear-mediated endothelial
calcium signals will exacerbate lesion formation in PAH. Therefore, the goal of this proposal is to determine the
interaction between TRPC4-dependent endothelial calcium signals and oscillatory shear stress as a driver of
occlusive remodeling in PAH. Determining the underlying basis of vascular remodeling in PAH may lead to a
novel class of PAH therapeutics for extending patient survival and improving quality of life. As a candidate
trained in the quantitative areas of computational modeling and animal physiology at the Center for Lung
Biology, I am well suited to investigate the determinants of vascular remodeling in PAH. Furthermore, the goals
of this award are aligned with my specific career goals of gaining research expertise, education, and
professional skills on my path to career independence. The proposed research plan takes advantage of the
robust institutional environment and considerable expertise in the pathophysiology of PAH. The project mentor,
Dr. Troy Stevens, and additional personnel are well known experts in the fields of endothelial biology, vascular
physiology, and pulmonary hypertension. Additionally, our state-of-the-art laboratories have the requisite
equipment to complete this work.

## Key facts

- **NIH application ID:** 10201722
- **Project number:** 5K25HL136869-05
- **Recipient organization:** UNIVERSITY OF SOUTH ALABAMA
- **Principal Investigator:** CHRISTOPHER MICHAEL FRANCIS
- **Activity code:** K25 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $159,548
- **Award type:** 5
- **Project period:** 2017-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201722

## Citation

> US National Institutes of Health, RePORTER application 10201722, TRPC4-mediated calcium signals accelerate vascular remodeling in pulmonary arterial hypertension (5K25HL136869-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10201722. Licensed CC0.

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