Serum osteoprotegerin is increased and predicts survival in idiopathic pulmonary arterial hypertension

Condliffe, Robin, Pickworth, Josephine A, Hopkinson, Kay, Walker, Sara J, Hameed, Abdul G, Suntharaligam, Jay, Soon, Elaine, Treacy, Carmen, Pepke-Zaba, Joanna, Francis, Sheila E, Crossman, David C, Newman, Christopher M H, Elliot, Charles A, Morton, Allison C, Morrell, Nicholas W, Kiely, David G and Lawrie, Allan (2012) Serum osteoprotegerin is increased and predicts survival in idiopathic pulmonary arterial hypertension. Pulmonary Circulation, 2 (1). pp. 21-7. ISSN 2045-8940

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Abstract

We previously reported that osteoprotegerin (OPG) is regulated by pathways associated with pulmonary arterial hypertension (PAH), and is present at elevated levels within pulmonary vascular lesions and sera from patients with idiopathic PAH (IPAH). Since OPG is a naturally secreted protein, we investigated the relationship between serum OPG and disease severity and outcome in patients with IPAH and animal models. OPG mRNA expression was measured in pulmonary artery smooth muscle cells (PASMC) from pulmonary arteries of patients with and without IPAH. Serum concentrations of OPG were measured in a retrospective and prospective group of patients. OPG levels were compared with phenotypic data and other putative PAH biomarkers. Prognostic significance was assessed and levels compared with healthy controls. Correlation of OPG and pulmonary vascular remodeling was also performed in rodent models of PAH. OPG mRNA was significantly increased 2-fold in PASMC isolated from explanted PAH lungs compared with control. Serum OPG concentrations were markedly elevated in IPAH compared with controls. In Cohort 1 OPG levels significantly correlated with mean right atrial pressure and cardiac index, while in Cohort 2 significant correlations existed between age-adjusted OPG levels and gas transfer. In both cohorts an OPG concentration above a ROC-derived threshold of 4728 pg/ml predicted poorer survival. In two rodent models, OPG correlated with the degree of pulmonary vascular remodeling. OPG levels are significantly elevated in patients with idiopathic PAH and are of prognostic significance. The role of OPG as a potential biomarker and therapeutic target merits further investigation.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 20 Jan 2014 16:02
Last Modified: 21 Apr 2020 22:32
URI: https://ueaeprints.uea.ac.uk/id/eprint/46181
DOI: 10.4103/2045-8932.94819

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