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S136 Potential therapeutic benefits of the human amniotic e
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S136 Potential therapeutic benefits of the human amniotic epithelium cell secretome during ex-vivo perfusion of donor lungs
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cysteine proteases was examined. Fluorogenic substrates analysed
include those for various inflammatory proteases including elas-
tase-like (MeOSuc-AAPV-AMC), MMPs (MCA-PLGL-Dpa-AR-
NH2), trypsin-like (Z-GGR-AMC) and chymotrypsin-like (Suc-
AAPF-AMC). Substrate hydrolysis by a relevant recombinant
enzyme (± inhibitors) was analysed as a control.
Results Data analysis indicates that alternative enzymes actively
hydrolyse substrates designed to be specific for one group of pro-
teases. Inhibitors specific for metallo, trypsin-like, chymotrypsin-
like and cysteine proteases all decreased elastase-like substrate
turnover (~10–50%). A similar trend was seen for chymotrypsin-
like substrate using metallo, trypsin-like and elastase-like protease
inhibitors (~10–40%).
Conclusion This investigation has suggested that there is signifi-
cant non-specific hydrolysis and cross-reactivity when fluorogenic
substrates are utilised to measure active proteases in complex bio-
logical samples. Thus, using such fluorogenic substrates may pro-
duce elevated readings, impacting on the accuracy of results
when such assays are used for clinical or research purposes.
S135 CIRCULATING METABOLITES IN CHRONIC
THROMBOEMBOLIC PULMONARY HYPERTENSION AND
CHRONIC THROMBOEMBOLIC PULMONARY VASCULAR
OCCLUSION
1
KI Zalewska,
1
EM Swietlik,
1
J Sanchez Hernandez,
1
JE Cannon,
1
D Taboada,
2
M Newnham,
2
C Hadinnapola,
2
NW Morrell,
1
MR T oshner,
1
J Pepke Zaba.
1
Papworth
Hospital NHS Foundation Trust, Cambridge, UK;
2
University of Cambridge, Cambridge, UK
10.1136/thoraxjnl-2016-209333.141
Introduction Recent studies have demonstrated that metabolomic
profiling can identify metabolites and pathways which may have
importance in the pathobiology of pulmonary arterial hyperten-
sion. However, the plasma metabolome in chronic thromboem-
bolic pulmonary hypertension (CTEPH) and chronic
thromboembolic vascular occlusions without pulmonary hyper-
tension (CTED) has not been well characterised.
Objective To profile circulating metabolites in CTEPH and
CTED and assess metabolite gradients across the pulmonary
circulation.
Methods In the patient group, multisite blood sampling was per-
formed at the time of right heart catheterisation. Blood samples
were collected from the superior vena cava, pulmonary artery
and radial artery.
Venous blood samples from patients were compared to healthy
controls to identify the metabolites present and to assess the dif-
ference between health and disease. Additionally, in the disease
group, transpulmonary gradients were assessed by analysis of fold
change in metabolite concentration between paired samples from
the pulmonary artery and radial artery.
Untargeted, semi-quantitative metabolic profiling of plasma
was performed using the Metabolon DiscoveryHD4™ platform
(Metabolon, NC, USA), utilising 2 ultra-high performance liquid
chromatography methods, coupled with tandem mass spectrome-
try. Kruskal-Wallis analysis was used to compare metabolites
between disease and control, with false discovery rate correction
for multiple testing.
Results The disease group included patients with a spectrum of
chronic pulmonary vascular occlusions (Table 1). A total of 1375
metabolites were detected in 70 venous plasma samples analysed
from 43 patients and 27 healthy controls. Amongst endogenous
metabolites, 266 showed a significant difference between disease
and control. In the disease group there were increases in
acylcarnitine metabolites, long chain fatty acids, polyamines, gly-
cogen metabolites and primary bile acid metabolites compared to
healthy controls. There was a reduction in lysolipids, plasmalo-
gens, aminosugars, branched chain amino acid metabolites, gluta-
thione metabolites and a number of steroids (Table 1). Analysis of
transpulmonary gradients revealed primarily a reduction in
metabolite concentration across the pulmonary circulation. This
included depletion of energy substrates, lysolipids, lysoplasmalo-
gens and acylcholines.
Conclusions This pilot study of circulating metabolites in patients
with CTEPH, CTED and healthy controls reveals differences
between health and disease in several biological pathways. Meas-
urement of the transpulmonary gradient of metabolites indicated
predominant clearance of circulating metabolites associated with
energy metabolism and cell turnover. These findings require con-
firmation in a larger population.
Abstract S135 Table 1 Study population and changes in
metabolite groups in venous blood of patients compared to healthy
controls
Chronic pulmonary vascular
occlusions (n = 43)
Controls
(n = 27)
Group demographics
Age (years) 58 (22–77) 44 (18–
75)
Sex (% male) 64 60
Patient group
Proximal CTEPH- treatment naive (n) 11
Distal CTEPH (n) 3
Proximal CTEPH- previous pulmonary
endarterectomy- residual PH (n)
11
Proximal CTEPH- previous pulmonary
endarterectomy, no residual PH (n)
10
Chronic thromboembolic vascular occlusions
without PH (n)
8
Changes in metabolites in disease
Acylcarnitines "
Long chain fatty acids "
Polyamines "
Glycogen metabolites "
Primary bile acid metabolites "
Lysolipids #
Plasmalogens #
Aminosugars #
Branched chain amino acids #
Glutathione metabolites #
Steroids #
S136 POTENTIAL THERAPEUTIC BENEFITS OF THE HUMAN
AMNIOTIC EPITHELIUM CELL SECRETOME DURING EX-
VIVO PERFUSION OF DONOR LUNGS
1
JW Mayes,
2
K Jiwa,
3
B Leaw,
3
J Tan,
3
S Lau,
1
L Borthwick,
1
A Andreasson,
1
J Dark,
3
G Jenkin,
3
R Lim,
1
AJ Fisher.
1
Newcastle University, Newcastle upon Tyne, UK;
2
Freeman
Hospital Newcastle upon Tyne NHS Hospitals, Newcastle upon Tyne, UK;
3
The Ritchie
Centre Monash University, Melbourne, Australia
10.1136/thoraxjnl-2016-209333.142
Introduction Ex-vivo lung perfusion (EVLP) is used to assess and
potentially recondition donor lungs that are not initially suitable
for transplantation. In a recent UK study, EVLP was associated
Spoken sessions
A80 Thorax 2016;71(Suppl 3):A1–A288
group.bmj.com on August 27, 2017 - Published by http://thorax.bmj.com/Downloaded from
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