# Functional Impact of Col18a1/Endostatin Variants in PAH

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $594,522

## Abstract

Project Summary
 It is well established that physiologic, imaging, and circulating biomarkers of right ventricular (RV)
dysfunction predict adverse outcomes in pulmonary arterial hypertension (PAH), yet our understanding of the
genetic, molecular, and cellular determinants of RV failure is nascent. Further, there is a clear clinical need to
identify targets directed at preserving and improving RV function in PAH.
 In this context, our global objectives are to identify and characterize novel molecular determinants and
clinical biomarkers of RV function and failure and define both their contribution to disease phenotype and their
potential for exploitation as therapeutic targets. Recognizing that cardiopulmonary dysfunction in PAH is linked
to pathologic changes in the microvasculature, we rationalized that circulating antagonists of microvascular
homeostasis could negatively impact on disease pathogenesis. We have demonstrated that endostatin (ES), a
potent inhibitor of angiogenesis (i.e., angiostatic factor), is elevated in PAH, associated with adverse
hemodynamic and functional status, and, importantly, w i t h increased mortality in idiopathic and connective
tissue disease associated PAH (IPAH and CTD-PAH, respectively). Further, we have identified multiple genetic
variants in the gene encoding ES (Col18a1) that are associated with potential altered protein function, protein
expression, cardiac function, and outcomes in PAH.
 This is a five-year grant proposal put forth jointly by a new and an established investigator on the role of
Col18a1 / ES on PAH. The objectives of the grant are to further define the relationship between ES and
cardiopulmonary structure and function in disease, to further define and characterize the molecular and
cellular effects of variants in the gene encoding ES (Col18a), and to provide necessary preclinical data on
the impact of ES antagonism as a potential therapeutic target in PAH.

## Key facts

- **NIH application ID:** 9843522
- **Project number:** 5R01HL132153-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** RACHEL L DAMICO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $594,522
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843522

## Citation

> US National Institutes of Health, RePORTER application 9843522, Functional Impact of Col18a1/Endostatin Variants in PAH (5R01HL132153-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9843522. Licensed CC0.

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