# The role of extracellular cAMP in the pathogenesis of pulmonary arterial hypertension

> **NIH NIH K01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2022 · $170,640

## Abstract

Project Summary
Pulmonary arterial hypertension (PAH) is a disease characterized by the progressive remodeling of
the distal pulmonary arteries, resulting in the loss of vascular cross-sectional area and elevated
pulmonary vascular resistance. Without intervention, PAH is usually progressive, leading to right
heart failure and death. Pulmonary vascular remodeling includes the proliferation and migration of
pulmonary artery smooth muscle cells, endothelial cells and fibroblasts. Several studies have shown
that increasing intracellular cyclic adenosine monophosphate (cAMP) levels result in a reduction of
vascular cells proliferation in vitro and in vivo, and it has recently been discovered that members of
the ATP-binding cassette (ABC) transporters family can actively transport cAMP out of cells.
Moreover, we recently reported secreted cardiomyocyte-cAMP into the extracellular space to be an
important paracrine factor in the myocardium that also protects the heart from adrenergically induced
hypertrophy and fibrosis. Extracellular cAMP is metabolized to adenosine, which activates its
receptors that are expressed in several cells. Because adenosine is known to be a potent inhibitor of
vascular remodeling (through its Gs protein-coupled receptors), we aim to study the presence of the
extracellular cAMP pathway in pulmonary vascular cells. Our goal is to attenuate pulmonary vascular
remodeling by using the extracellular cAMP pathway as a therapeutic approach to reverse the
pathological changes in PAH. The specific aims of this proposal are: 1) to define the presence of the
extracellular cAMP pathway in pulmonary artery cells, 2) to evaluate the effects of extracellular cAMP
on vascular cells proliferation and migration, as well as determining its mechanism, 3) to assess the
effects of endogenous secreted-cAMP in pulmonary vascular cells and 4) to investigate the impact of
extracellular cAMP infusion in in vivo models of PAH. Defining the presence and the mechanisms of
the extracellular cAMP pathway and its physiological consequences will be of great relevance in the
analysis of the PAH disease. Targeting the extracellular cAMP pathway might be a useful strategy to
prevent and treat pulmonary hypertension.

## Key facts

- **NIH application ID:** 10499575
- **Project number:** 7K01HL135474-05
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Yassine Sassi
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $170,640
- **Award type:** 7
- **Project period:** 2018-03-20 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499575

## Citation

> US National Institutes of Health, RePORTER application 10499575, The role of extracellular cAMP in the pathogenesis of pulmonary arterial hypertension (7K01HL135474-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10499575. Licensed CC0.

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