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Cardiovascular Journal of Africa • ABSTRACTS – SA HEART
®
CONGRESS 2019
S43
AFRICA
S100 calcium-binding protein B and silent ischaemic events: Indicators of emergent brain-heart pathology
Nina Truter*, Leone Malan
#
and M. Faadiel Essop*
*Faculty of Medicine and Health Sciences, University of Stellenbosch and Tygerberg Hospital, Bellville, South Africa.
#
Hypertension in Africa Research Team
(HART), North-West University, Potchefstroom, South Africa
Introduction:
As cardiovascular disease (CVD) is the leading global cause of mortality, earlier diagnosis is needed. Although previous studies have identified
traditional risk factors (e.g. inactivity, poor diet, smoking and obesity), recent studies highlight the role of psychosocial stress. The brain-heart axis is thus an
emerging concept which better explains the link between stress and CVD onset. This study aims to elucidate the correlation between S100 calcium-binding
protein B (S100B; brain and cardiac ischaemia marker); glial cell line-derived neurotrophic factor (GDNF; neuroprotective marker) and a known clinical CVD
marker (silent ischaemic events), which may improve our understanding of the brain-heart axis and emerging pathology.
Methods:
This cross-sectional study consisted of a bi-ethnic cohort of urban-dwelling male and female teachers (n=409) with similar socio-economic status
(North-West province). Silent ischaemic events were recorded using a 24-hour electrocardiograph and immunoassays were performed to evaluate S100B
and GDNF serum levels. To determine group differences, statistical analyses were performed using ANCOVAs and partial correlations completed using clinical
marker data.
Results:
Serum S100B and GDNF levels differed significantly between men and women (0.04 vs. 0.05g/L; p<0.01 and 572.48 vs. 280.63pg/mL; p<0.05,
respectively) independent of covariates. Differences were also found between African and Caucasian men regarding the number (11.72 vs. 0.84; p<0.001)
and maximum duration of silent ischaemic events (64.04 vs. 4.77 minutes; p<0.05) as well as S100B serum levels (0.05 vs. 0.04; p<0.001). A significant positive
correlation was observed between S100B and the number and duration of ischaemic events in men (0.37; p<0.01 and 0.31; p<0.01, respectively). S100B also
correlated with ischaemic event duration in women (0.24; p<0.05).
Conclusion:
Silent ischaemic events may be predictive of ongoing glial cell apoptosis, potentially supporting a link between glial cell plasticity and the heart.
This study provides a deeper understanding as to the bidirectional communication between the heart and the brain.
Clinical characteristics of idiopathic dilated cardiomyopathy in Johannesburg
Nqoba Tsabedze*, Dineo Mpanya*, Claude Bailly
#
, Sacha Grinter*, Engela Fouche*, Samantha Nel* and Pravin Manga*
*Division of Cardiology, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Charlotte Maxeke Johannesburg Academic
Hospital, Johannesburg, South Africa.
#
Division of Human Genetics, National Health Laboratory Services and School of Pathology, Faculty of Health Sciences,
University of the Witwatersrand, Johannesburg, South Africa
Introduction:
Idiopathic dilated cardiomyopathy (IDCM) is one of the common causes of heart failure in sub-Saharan Africa. Affected individuals present
with heart failure with reduced ejection fraction with no primary or secondary cause. In sub-Saharan Africa, the clinical manifestations and the prevalence of
the genetic contribution to this disease are unknown. We aim to describe the clinical features of patients presenting with heart failure of unknown origin and
to exclude primary and secondary causes to confirm IDCM.
Methods:
Since July 2015, all inpatients and outpatients with dilated cardiomyopathy (DCM), without an aetiology presenting to the division of cardiology
at the Charlotte Maxeke Johannesburg Academic Hospital were screened. These patients were systematically investigated to exclude primary and secondary
causes of heart failure. This included screening on history, clinical examination, biochemical investigations, coronary angiography to exclude ischaemic heart
disease and performing cardiac magnetic resonance imaging to exclude primary myocardial diseases and infiltrative diseases. A clinical geneticist further
interrogated patients with IDCM to obtain a history of familial dilated cardiomyopathy.
Results:
We screened 288 patients with heart failure of unknown origin. One hundred patients were recruited into the study and were confirmed to have
idiopathic DCM. This cohort consists of 92 Black patients of which 66 were males with a mean age of 47.1 ± 12.8 years.
Conclusion:
IDCM is prevalent among young adult Black males with a high mortality rate, 18% of affected patients demise within a year. A genetic aetiology
should thus be considered in young Black patients presenting with IDCM.
Protein phosphatase 2A and protein dephosphorylation in the heart’s response to ischaemia/reperfusion
Derick Van Vuuren, Charlize White, Lutendo Maumela and John Lopes
University of Stellenbosch and Tygerberg Hospital, Bellville, South Africa
Introduction:
Treatment of myocardial infarction relies primarily on limiting the duration of ischaemia. Cardioprotective interventions, however,
prove that injury can be minimised by the modulation of intracellular signalling pathways which are largely dependent on reversible protein phosphorylation.
Relatively little is known regarding the importance of protein dephosphorylation, mediated by protein phosphatases, in this setting. The aim of this study
was therefore to determine the effect of ischaemia on protein phosphatase activity, specifically the role and importance of protein phosphatase 2A (PP2A) in
ischaemia.
Methods:
Cardiac H9c2 cells were exposed to 2 hours of simulated ischaemia (SI) in the presence and absence of either an inhibitor (Cantharidin, 2µM or
5µM) or activator (FTY720, 1µM or 5µM) of PP2A. In addition, an isolated working mouse heart model was exposed to 20 minutes of global ischaemia and
either 10 or 60 minutes of reperfusion in the presence or absence of another PP2A inhibitor, okadaic acid (OA, 50nM), administered prior to ischaemia.
Results:
Non-specific determination of protein phosphatase activity in H9c2 cells at the end of SI showed that SI exerted no effect on overall phosphatase
activity. Pharmacological modulation of PP2A also failed to exert an effect on SI-induced cell death. Despite this, OA administration reduced infarct size in
isolated mouse hearts exposed to ischaemia/reperfusion. Initial phosphoproteomic results show that PP2A inhibition, prior to ischaemia/reperfusion, is
associated with a change in the phosphorylation of 58 proteins in the mouse heart. These proteins are involved in several processes, including cytoskeletal,
mitochondrial and calcium handling dynamics.
Conclusion:
Although our non-specific data indicate that the protein phosphatases are not modulated by ischaemia/reperfusion, specific focus on PP2A
reveals the dynamic nature of protein phosphorylation in response to ischaemia and further highlights the fact that protein phosphatases, such as PP2A,
remain potentially interesting targets for cardioprotective interventions.