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Reduced plasma levels of small HDL particles transporting fibrinolytic proteins in pulmonary arterial hypertension

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Title: Reduced plasma levels of small HDL particles transporting fibrinolytic proteins in pulmonary arterial hypertension
Authors: Harbaum, L
Ghataorhe, P
Wharton, J
Jimenez, B
Howard, L
Gibbs, S
Nicholson, J
Rhodes, C
Wilkins, M
Item Type: Journal Article
Abstract: Background Aberrant lipoprotein metabolism has been implicated in experimental pulmonary hypertension, but the relevance to patients with pulmonary arterial hypertension (PAH) is inconclusive. Objective To investigate the relationship between circulating lipoprotein subclasses and survival in patients with PAH. Methods Using nuclear magnetic resonance spectroscopy, 105 discrete lipoproteins were measured in plasma samples from two cohorts of patients with idiopathic or heritable PAH. Data from 1124 plasma proteins were used to identify proteins linked to lipoprotein subclasses. The physical presence of proteins was confirmed in plasma lipoprotein subfractions separated by ultracentrifugation. Results Plasma levels of three lipoproteins from the small high-density lipoprotein (HDL) subclass, termed HDL-4, were inversely related to survival in both the discovery (n=127) and validation (n=77) cohorts, independent of exercise capacity, comorbidities, treatment, N-terminal probrain natriuretic peptide, C reactive protein and the principal lipoprotein classes. The small HDL subclass rich in apolipoprotein A-2 content (HDL-4-Apo A-2) exhibited the most significant association with survival. None of the other lipoprotein classes, including principal lipoprotein classes HDL and low-density lipoprotein cholesterol, were prognostic. Three out of nine proteins identified to associate with HDL-4-Apo A-2 are involved in the regulation of fibrinolysis, namely, the plasmin regulator, alpha-2-antiplasmin, and two major components of the kallikrein–kinin pathway (coagulation factor XI and prekallikrein), and their physical presence in the HDL-4 subfraction was confirmed. Conclusion Reduced plasma levels of small HDL particles transporting fibrinolytic proteins are associated with poor outcomes in patients with idiopathic and heritable PAH.
Issue Date: 26-Nov-2018
Date of Acceptance: 12-Nov-2018
URI: http://hdl.handle.net/10044/1/66338
DOI: https://dx.doi.org/10.1136/thoraxjnl-2018-212144
ISSN: 1468-3296
Publisher: BMJ Publishing Group
Journal / Book Title: Thorax
Copyright Statement: © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: British Heart Foundation
British Heart Foundation
Funder's Grant Number: RG/10/16/28575
FS/15/59/31839
Keywords: primary pulmonary hypertension
1103 Clinical Sciences
Respiratory System
Publication Status: Published online
Online Publication Date: 2018-11-26
Appears in Collections:Division of Surgery
National Heart and Lung Institute
Department of Medicine
Faculty of Medicine



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