# Role of IGF axis in pulmonary hypertension

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $740,403

## Abstract

Project Summary
Pulmonary arterial hypertension (PAH) in children or adults is a progressive and fatal disease characterized by
sustained elevations of pulmonary artery pressure of unknown etiology. Pulmonary arterial smooth muscle cell
(PASMC) and endothelial (PAEC) proliferation that ultimately lead to heart failure are key components of the
pulmonary hypertension pathophysiologic response. Our current diagnostic/prognostic state of art
(echocardiography, 6 minute walk test and NTproBNP levels) are not lung/vascular specific, have poor diagnostic
correlation, confounded by systemic diseases and are not applicable to all ages. We now have pilot data that
IGFBP dysregulation is a significant circulating predictor of PAH severity and survival. The overall goal of this
proposal is to elucidate the in vitro and in vivo mechanistic role of IGF axis in PAH and potential as a
circulating new measure of PAH therapeutic response and survival. The significance of the proposed
studies is that by linking dysregulation of the IGF pathway to pulmonary endothelial/smooth muscle cellular
proliferation, patient survival, and response to treatment, a critical mechanism of PAH pathobiology is revealed
and provides the basis for new therapeutic, diagnostic and prognostic strategies in PAH. Using available
pediatric (University of Colorado), adult (Vanderbilt) and multicenter (PAHBiobank) cohorts and isolated PAEC
and PASMC from the PHBI, our overall goal will be addressed in the following specific aims: 1) Determine if
IGF and IGFBPs are PAH predictors of severity, survival and response to therapy in children and adults. 2)
Identify genetic variants associated with circulating levels of IGFs and IGFBPs and their relationship with clinical
severity and survival. 3) Defining the contribution of the IGFBPs to the phenotypic responses of pulmonary
vascular cells (PAEC and PASMC) from PAH and normal donors. If validated in this study, dysregulation of the
IGF pathway could fill an important gap in clinical care and serve as a new opportunity for a more thorough
understanding of PAH pathobiology and development of new therapeutic targets.

## Key facts

- **NIH application ID:** 10050243
- **Project number:** 1R01HL150070-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ALLEN D EVERETT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $740,403
- **Award type:** 1
- **Project period:** 2020-06-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10050243

## Citation

> US National Institutes of Health, RePORTER application 10050243, Role of IGF axis in pulmonary hypertension (1R01HL150070-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10050243. Licensed CC0.

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