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@article{Harbaum:2019:10.1136/thoraxjnl-2018-212144,
author = {Harbaum, L and Ghataorhe, P and Wharton, J and Jimenez, B and Howard, L and Gibbs, S and Nicholson, J and Rhodes, C and Wilkins, M},
doi = {10.1136/thoraxjnl-2018-212144},
journal = {Thorax},
pages = {380--389},
title = {Reduced plasma levels of small HDL particles transporting fibrinolytic proteins in pulmonary arterial hypertension},
url = {http://dx.doi.org/10.1136/thoraxjnl-2018-212144},
volume = {74},
year = {2019}
}

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TY  - JOUR
AB  - 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.
AU  - Harbaum,L
AU  - Ghataorhe,P
AU  - Wharton,J
AU  - Jimenez,B
AU  - Howard,L
AU  - Gibbs,S
AU  - Nicholson,J
AU  - Rhodes,C
AU  - Wilkins,M
DO  - 10.1136/thoraxjnl-2018-212144
EP  - 389
PY  - 2019///
SN  - 1468-3296
SP  - 380
TI  - Reduced plasma levels of small HDL particles transporting fibrinolytic proteins in pulmonary arterial hypertension
T2  - Thorax
UR  - http://dx.doi.org/10.1136/thoraxjnl-2018-212144
UR  - http://hdl.handle.net/10044/1/66338
VL  - 74
ER  -

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