# Clinical and mechanistic role of HDGF in pulmonary hypertension

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $588,248

## 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 are key components of the pulmonary hypertension
pathophysiologic response. Although the number of vasodilator drugs has increased, still 20-30% of patients do
not respond and non-responders have a poor prognosis eventually requiring lung transplantation1-4. 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. In essence, we lack simple, minimally invasive more lung/vascular specific, objective, repeatable,
generalizable and less expensive measures of PAH to improve outcomes. We now have pilot data that the
pulmonary angiogenic protein, hepatoma derived growth factor (HDGF), 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 HDGF 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 HDGF to pulmonary
endothelial/smooth muscle cellular proliferation, patient survival, and response to treatment, a critical step in the
function of HDGF 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 HDGF is a PAH predictor of severity, survival and response to therapy in children
and adults. 2) Determine if circulating HDGF levels are affected by specific FPAH gene defects and in unaffected
carriers, and determine if human HDGF genomic variants are associated with IPAH. 3) Defining the contribution
of HDGF to the phenotypic responses of pulmonary vascular cells (PAEC and PASMC) from PAH and normal
donors. If validated in this study, HDGF could fill an important gap in the current clinical care and treatment of
PAH patients for improved risk stratification, assessment of response to therapy, clinical worsening exceeding
current clinical care measures.

## Key facts

- **NIH application ID:** 9850984
- **Project number:** 5R01HL135114-04
- **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:** $588,248
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850984

## Citation

> US National Institutes of Health, RePORTER application 9850984, Clinical and mechanistic role of HDGF in pulmonary hypertension (5R01HL135114-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9850984. Licensed CC0.

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