CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 1, January/February 2013
288
AFRICA
hypertensive HF had higher levels compared with those with hyper-
tensive LVH (134.7
±
57.3 vs 23.0
±
8.3 ng/ml,
p
=
0.000). There
was however no significant difference between NT-proBNP levels
when hypertensive subjects with LVH were compared with those
without LVH (
p
=
0.68) but those with heart failure had significantly
higher NT-proBNP levels compared with hypertensives with LVH (
p
<
0.000). ST2 has a stronger correlation with clinical and echocardi-
ograhic parameters compared to NT-proBNP. Serum ST2 also corre-
lated well with NT-proBNP (
r
=
0.41,
p
<
0.000). In the assessment
of the hypertensive heart disease spectrum, ST2 correlates well with
NT-proBNP and has proven to be a better marker.
Conclusions:
Plasma ST2 levels appear to be a very useful marker
in differentiating the different spectra of hypertension–hypertensive
heart disease and may hold a future role in this regard.
1226: GENE EXPRESSION PROFILES IN ENGINEERED
CARDIAC TISSUES RESPOND TO MECHANICAL LOAD-
ING AND INHIBITION OF TYROSINE KINASES
Bradley Keller, Fei Ye, Fang Ping Yuan, Xiaohong Li, Joseph Tinney
University of Louisville, USA
Background
: Several formulations for engineered cardiac tissue
(ECT) have emerged that incorporate stem cells or immature
cardiomyocytes into three-dimensional (3D) constructs. These ECTs
mature
in vitro
, acquire the features of mature cardiac muscle, appear
to involve the p38MAP kinase (p38MapK) pathway, and respond to
mechanical load with increased proliferation and maturation. We
hypothesised that global ECT gene expression patterns are sensitive
to mechanical loading conditions and tyrosine kinase inhibitors.
Methods
: We generated 3D ECTs from immature rat embryo heart
cells, as previously published, and then treated constructs after five
days in culture for 48 hours with mechanical stretch (5%, 0.5 Hz)
and/or the following selective inhibitors (birb796 for p38MapK,
CI10404 for ERK1/2, or SP60025 for JNK). RNA was isolated from
three sets of experiments and assayed using a standard Agilent rat
4x44k V3 micro-assay. The Ingenuity Systems Pathway analyser
was used to analyse data from individual experiments, pooled within
groups and between groups.
Results
: Changes in gene expression in response to mechanical
stretch and/or inhibitors were recorded. As anticipated, top pathways
altered in response to these stimuli included cellular development,
cellular growth and proliferation; tissue development; cell death, cell
signalling and small-molecule biochemistry, as well as numerous
other pathways.
Conclusion
: ECTs display a broad spectrum of altered gene expres-
sion in response to mechanical load and/or tyrosine kinase inhibition,
reflecting the complex regulation of proliferation, differentiation and
architectural alignment during ECT maturation.
1381: CARDIOPROTECTVIE EFFECT OFACE2ACTIVATOR
ON LEFTVENTRICULAR DYSFUNCTION SECONDARY TO
PRESSURE OVERLOAD IN THE RAT
Zen-Kong Dai, Mian-Shin Tan, Jiunn-Ren Wu, I-Chen Chen, Jong-
Hau Hsu
Department of Paediatrics, Kaohsiung Medical University Hospital,
Kaohsiung Medical University, Taiwan
Objectives:
The RAS (renin–angiotensin system) is activated after
myocardial infarction, and RAS blockade with angiotensin convert-
ing enzyme inhibitors or angiotensin receptor blockers slows but
does not completely prevent progression to heart failure. In contrast,
angiotensin converting enzyme 2 (ACE2)/angiotensin-(1-7) [Ang-
(1-7)]/Mas is recognised as a counter-regulatory axis. Little is known
about the role of ACE2 in cardiac dysfunction secondary to pressure-
overload.
Hypothesis:
In pressure overload-induced cardiac dysfunction, we
hypothesised that cardiac expressions of ACE 2 and Ang-(1-7) are
down-regulated, and an ACE2 activator can attenuate the develop-
ment of left ventricular dysfunction through ACE2/Ang-(1-7)/recep-
tor mas axis.
Methods and Results:
In the Wistar rats subjected to ascending
aortic banding (AOB), starting 29 days after banding, banded rats
were treated with DIZE (ACE2 activator) at a dose of 15 mg/kg/
day intra-peritoneally or vehicle for 14 days. Subsequently, there
was down-regulated cardiac expression of Ang-(1-7) in AOB for
42 days compared to sham-operated rats. DIZE could significantly
decrease the mean pulmonary arterial pressure and mean left atrial
pressure, and attenuate left ventricular remodelling, respectively,
when compared with the vehicle controls. In addition, DIZE caused
up-regulated expression of ACE2, receptor mas and endothelial nitric
oxide synthase in 42-day banded rats.
Conclusions:
These results indicate that activation of ACE2 may
provide preventive potential for attenuating the development of left
ventricular dysfunction secondary to pressure overload. Further
translational study, including oxidative stress in humans, is needed to
substantiate the findings.
1422: ARG72 VARIANT OF p53 CODON 72 FUNCTIONAL
POLYMORPHISM AND RISK OF CORONARY ARTERY
DISEASE IN A SOUTH AFRICAN POPULATION
Sajidah Khan
1
, Alisa Phulukdaree
2
, Devapregasan Moodley
2
, Anil
Chuturgoon
2
1
Department of Cardiology, University of KwaZulu-Natal, Durban,
South Africa
2
Department of Medical Biochemistry, University of KwaZulu-Natal,
Durban, South Africa
Introduction:
Atherogenic stimuli induce DNA damage through
increased oxidative stress. DNA damage leads to increased expres-
sion of p53, a pro-apoptotic gene whose principal function is to
protect cells from malignant transformation. p53 is thought to
contribute to vascular disease by increasing apoptosis of macrophag-
es and smooth muscle cells in advanced atherosclerotic lesions,
rendering them vulnerable to rupture. More recently, p53 has been
shown to regulate genes involved in lipid and carbohydrate metabo-
lism. Polymorphisms of the p53 gene have been associated with
increased susceptibility to coronary artery disease (CAD).
Methods:
A common polymorphism in the p53
gene, Pro72Arg
(rs1042522), results in the substitution of arginine (Arg) for proline
(Pro) at codon 72 in the amino acid sequence of the protein. The
Arg72- has been reported as a more potent inducer of apoptosis than
the Pro72 variant. One hundred young (mean age 37.5 years, range
24–45) male Asian Indian patients with CAD confirmed at angiog-
raphy were compared with 100 healthy control subjects matched for
age, gender and ethnicity. Polymorphic variants were assessed by
polymerase chain reaction–restriction fragment length polymorphism.
Results:
The frequency of p53 codon 72 genotypes were 28% Arg/
Arg, 48% Arg/Pro and 24% Pro/Pro in CAD patients compared to
30, 61 and 9%, respectively, in the control group. A significantly
higher frequency of the p53 Arg72 allele was found in CAD patients
compared to the p53 Pro72 allele (52 vs 40%,
p
<
0.0121, OR
=
1.659, 95% CI: 1.116–2.467). Lipid and glycaemic indices were not
significantly influenced by the p53 genotypic variants.
Conclusion:
The p53 Arg72 allele is associated with increased risk
of CAD in this cohort of Asian Indian male patients with premature
CAD.
1458: EFFECT OF HUMAN UMBILICAL CORD BLOOD-
DERIVED MESENCHYMAL STEM CELL TRANSFUSION
IN MONOCROTALINE-INDUCED PULMONARY HYPER-
TENSION IN A RAT MODEL
Young Mi Hong
1
, Kwan Chang Kim
2
, Min-Sun Cho
3
, Yoon Sun
Yang
4
, Wonil Oh
4
, Soo Jin Choi
4
1
Department of Paediatrics, Ewha Womans University, Seoul, Korea
2
Department of Thoracic and Cardiovascular Surgery, Ewha Womans
University, Seoul, Korea
