# Mural cells contribution to vascular remodeling in flow induced pulmonary hypertension

> **NIH NIH K08** · BOSTON CHILDREN'S HOSPITAL · 2024 · $167,940

## Abstract

Project Summary/Abstract: Pulmonary arterial hypertension (PAH) is a progressive vascular disorder
characterized by narrowing and remodeling of the distal arterioles. Current treatment options are unable to
prevent disease progression, leading to a median survival time of five years after diagnosis. Therefore, there is
an urgent need to develop new disease-modifying therapies. Increased pulmonary blood flow is known to
stimulate vascular remodeling in patients with congenital heart disease (CHD) and after major lung resection,
although the underlying mechanism is unclear. Patients with left-to-right shunts such as ventricular septal defects
and atrioventricular canal defects are at high risk for PAH. A “second hit” in the context of pulmonary
overcirculation, such as hypoxia, may lead to irreversible vascular remodeling and disease progression. Current
rodent models of flow-induced pulmonary hypertension (PH) such as the left pneumonectomy and SUGEN rat
do not fully recapitulate patients' physiological conditions. To improve patient outcomes, animal models more
representative of patients are needed, along with a better understanding of the underlying molecular
mechanisms.
 My goal is to generate a novel animal model to study flow-induced PH. Establishing a murine model of
PH that mimics patients with CHD will enable the development of therapeutics capable of reversing flow-induced
vascular remodeling. The second goal of this proposal is to discover key insights into the response of smooth
muscle cells (SMCs) to vascular remodeling from increased pulmonary blood flow. Specifically, the aims of this
proposal are to 1. Develop a new mouse model of flow-induced PH that better represents patients' physiological
conditions, 2. Describe the contribution and underlying mechanisms in which SMCs contribute to shear stress-
induced vascular remodeling, and 3. Discover novel therapeutic approaches for patients with PAH-CHD.

## Key facts

- **NIH application ID:** 10985482
- **Project number:** 1K08HL171843-01A1
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Timothy Klouda
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $167,940
- **Award type:** 1
- **Project period:** 2024-09-20 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985482

## Citation

> US National Institutes of Health, RePORTER application 10985482, Mural cells contribution to vascular remodeling in flow induced pulmonary hypertension (1K08HL171843-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10985482. Licensed CC0.

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