CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 1, January/February 2013
AFRICA
287
regarded as an alternative source of bone marrow-derived mesen-
chymal stem cells. hUCB-MSCs have recently been studied for
evaluation of their potential as a source of cell therapy. The purposes
of this study were to investigate changes of pulmonary pathology,
haemodynamics and gene expression of caspase 3, Bcl2, vascular
endothelial growth factor (VEGF), interleukine (IL)-6, and tumour
necrosis factor (TNF)-
α
in monocrotaline (MCT)-induced PAH rat
models after hUCB-MSCs transfusion.
Methods
The rats were grouped as follows: control group (C group),
subcutaneous injection of saline; M group, subcutaneous injection of
MCT (60 mg/kg); and hUCB-MSCs transfusion (U group). hUCB-
MSCs (3
×
10
6
/ml/cm
2
) were transfused by intraperitoneal injection
one week after MCT injection.
Results
: The mean right ventricular pressure (RVP) significantly
decreased in the U group compared with the M group in weeks two
and four. RV weight and the ratio of RH/LH
+
septum significantly
decreased in the U group compared to the M group. The number of
muscular pulmonary arterioles significantly decreased in the U group
compared with the M group in weeks two and four. Medial wall
thickness of the pulmonary arteriole significantly decreased in the U
group compared to the M group in week two. Gene expressions of
caspase-6, Bcl-2, VEGF, IL-6 and TNF-
α
significantly decreased in
week four in the U group compared with the M group.
Conclusion
: After hUCB-MSCs transfusion there was improvement
of RVH, mean RV pressure and survival rate. Decreases in several
gene expressions were observed. Additional research on the dose
and frequency of hUCB-MSCs infusion is needed to determine the
optimal parameters for PAH treatment
.
1194: CHANGES OF CASPASE 3, BCL2, AND VASCU-
LAR ENDOTHELIAL GROWTH FACTOR AFTER BONE
MARROW CELL TRANSFUSION IN RATS WITH MONO-
CROTALINE-INDUCED PULMONARY HYPERTENSION
Kwan Chang Kim, Min-Sun Cho, Young Mi Hong
Ewha Womans University, Seoul, South Korea
Background:
Pulmonary arterial hypertension (PAH) is difficult to
treat and is characterised by increased pulmonary arterial pressure,
right heart dysfunction, lung vascular remodelling and death. Bone
marrow-derived mesenchymal stem cell therapy has provided an
alternative treatment for ailments of various organs by promoting
regeneration at the site of pathology. The purposes of this study were
to investigate changes of pulmonary pathology, haemodynamics and
gene expressions of Caspase 3, Bcl2, and vascular endothelial growth
factor (VEGF) in monocrotaline (MCT)-induced PAH rat models
after bone marrow cell (BMC) transfusion. The rats were grouped as
follows: control group; M group, subcutaneous injection of monocro-
taline (MCT); BMC transfusion (B group). BMC were transfused by
intravenous injection in the tail one week after MCT injection.
Results:
The mean right ventricular pressure (RVP) significantly
decreased in the B group compared with the M group in weeks two
and four. RV weight significantly decreased in the B group compared
to the M group in weeks two and four. The ratio of medial thicken-
ing of the pulmonary artery was significantly decreased in the B
group compared with the M group in week two. The number of
muscular pulmonary arterioles significantly decreased in the B group
compared with the M group in week four. The number of muscular
pulmonary arterioles increased in the M group compared with the C
group in weeks two and four. Gene expressions of Caspase 3, Bcl2,
and VEGF significantly increased in the M group compared with the
C group and significantly decreased from week two in the B group
compared with the M group.
Conclusion:
After BMC transfusion, there was improvement of RVH
and mean RV pressure. Decreases in several genes were observed.
Additional research on the dose and frequency of BMC infusion is
needed to better determine the optimal parameters for PAH treat-
ment.
1214: EXOME SEQUENCING IN SYNDROMIC PATIENTS
WITH CONGENITAL HEART DISEASE: PERFORMING A
TRIO ANALYSIS
Jacoba Louw
1
, Yaojuan Jia
2
, Anniek Corveleyn
2
, Marc Gewillig
1
,
Koenraad Devriendt
2
1
Paediatric and Congenital Cardiology, University Hospitals Leuven,
Leuven, Belgium
2
Centre for Human Genetics, University Hospitals Leuven, Leuven,
Belgium
Background:
Congenital heart defects (CHD) are a major cause of
infant morbidity and mortality. Reaching an aetiological diagnosis
in patients with a syndromic heart defect is important, not only to
gain insight into their pathogenesis and for genetic counselling on
recurrent risks, but especially with regard to providing information
on the future prognosis, based on knowledge of the natural course of
the disorder. In syndromic cases, an exact aetiological diagnosis can
be reached in an estimated 50 to 60% of patients, following careful
clinical evaluation, complemented by various genetic tests, includ-
ing array-CGH. With the advent of exome sequencing, it is now
feasible to perform a trio analysis, i.e. sequencing of the coding parts
of the genes in both parents and the child, where only the child is
affected, in order to identify a candidate gene. For syndromic cases,
we hypothesised that these patients have a thus far unrecognised
monogenic condition responsible for both the intelligence deficit
and the heart defect. Since the majority of syndromes featuring CHD
are dominant, it is likely that at least in a subset of these, a
de novo
dominant mutation is present.
Methods:
In-solution capture (Nimblegen target-enrichment system)
and sequencing will be done on the Illumina HiSeq2000 platform
(Genomics Core KULeuven/UZLeuven). Possible causal mutations
will be confirmed by traditional Sanger sequencing.
Results and Conclusion:
Preliminary results on exome sequencing
in trios on the child presenting with congenital heart disease, dysmor-
phic features and mental retardation will be discussed.
1218: COMPLEMENTARY ROLES OF THE NOVEL
BIOMARKER ST2 AND NT-proBNP IN AFRICAN HYPER-
TENSIVE SUBJECTS
Dike Ojji
1,5
, Sandrine Lecour
2
, Lydia Lacerda
3
, Soji BillyRose
Adeyemi
4
, Karen Sliwa
2,6
1
Cardiology Unit, Department of Medicine, University of Abuja
Teaching Hospital, Nigeria
2
Hatter Institute for Cardiovascular Research in Africa, Faculty of
Health Sciences, University of Cape Town, South Africa
3
University of Stellenbosch, Stellenbosch, South Africa
4
Department of Medical Laboratory Sciences, University of Abuja
Teaching Hospital, Gwa
5
Department of Medicine, Faculty of Health Sciences, University of
Cape Town, South Africa
6
Soweto Cardiovascular Research Unit, University of the
Witwatersrand, Johannesburg, South Africa
Background:
AlthoughNT- pro brain natriuretic peptide (NT-proBNP)
levels have been shown to differentiate hypertensive left ventricular
hypertrophy (LVH) without heart failure (HF) from hypertensive
HF due to systolic and/or diastolic dysfunction, it has not been very
helpful in differentiating hypertensive subjects with LVH from those
without. We therefore decided to see the complementary role of solu-
ble ST2, a novel biomarker of biomechanical strain.
Methods:
This was a prospective cohort study. Echocardiography
was performed on all subjects. LVH was considered present when
left ventricular mass, indexed for height
2.7
, was greater than 46.2 g/
m
2.7
in women and 49.2 g/m
2.7
in men. Plasma ST2 and NT-proBNP
was measured using electrochemiluminescence-type immunoassay.
Results:
Of 210 subjects studied, 42.9% were female, and the mean
age of the study cohort was 50.3
±
11.3 years. Hypertensive subjects
with LVH had higher concentrations of ST2 compared to those with-
out LVH (23.0
±
8.3 vs 14.5
±
4.9 ng/ml,
p
=
0.001) and those with
