Cardioprotection Group

Overview

Cardioprotection Group

Overview

The main objective of the Cardioprotection Group is the delineation of novel cardioprotective signalling pathways that can be activated to limit cell death in various pathophysiological conditions, such as heart failure, myocardial infarction or diabetes.

Group Members

Prof Sandrine Lecour (Principal Investigator)

Camelita Abrahams (PhD Student)

Siddiqah George (PhD Student)

Nkanyiso Hadebe (PhD Student)

Kodogo Vitaris (PhD Student)

Xoliswa Nxele (PhD Student)

Peter Hudson (MSc Student)

Rentia Lourens (Hons Student)

Dr Aqeela Imamdin (Affiliated Member)

Dr Gaurang Desphande (Affiliated Member)

Dr Frederic Nduhirabandi (Affiliated Member)

Dr Dike Ojji (Affiliated Member)

Dr Nicholas Woudberg (Affiliated Member)

Current Projects

Innate immunity and cardioprotection

An important emerging concept is that the heart has an innate immune-related protective mechanism. In the context of ischemic heart disease, our latest research showed that Tumor Necrosis Factor alpha (TNF-alpha), a major player of the immune system, initiated the activation of a cardioprotective signalling pathway that involved the activation of the signal transducer and activator of transcription 3 (STAT-3). We have named this path the SAFE (Survivor Activating Factor Enhancement) pathway (Lecour, J Mol Cell Cardiol, 2009, Hadebe et al, Basic Res Cardiol, 2018). Our current research aims to better characterize this novel path which paves a new way for the development of novel drug therapies against ischemic heart disease.

Red wine and cardioprotection

Moderate and regular consumption of red wine (2-3 glasses/day) confers cardioprotection. However, the exact components found in the wine which can account for this protective effect still need to be delineated (Opie and Lecour, Eur Heart J, 2007). We have recently investigated the cardiovascular role of 2 biogenic amines (ethanolamine and melatonin) found in red wine and we have demonstrated that both amines, given at a concentration found in red wine, can protect against ischemic heart disease (Kelly et al, Basic Res Cardiol, 2010; Lamont et al, J Pineal Res, 2010). Using genetically modified animals, our current research aims to delineate the cellular mechanisms involved in red wine/melatonin-induced cardioprotection.

High density lipoproteins and cardioprotection

In 2002, we were first to report that sphingosine-1 phosphate can protect against reperfusion injury (Lecour et al, J Mol Cell Cardiol, 2002). Sphingosine-1 phosphate is a major component of high density lipoproteins, often referred to as the “good” cholesterol. Using various reconstituted HDL (synthesized by our research collaborators in Switzerland), we have been able to demonstrate that sphingosine-1 phosphate content in HDL contributes to the cardioprotective effect of HDL against reperfusion injuries (Brulhart-Meynet MC et al, Plos One, 2015). With the recent acquisition of the Lipoprint system, we are now able to explore the subfractions of lipoproteins in the presence of different cardiovascular risk factors such as hypertension, obesity, lack of exercise (see Woudberg et al, J Obes, 2019; Lipids Health Dis, 2018). Our current research aims at exploring the association between a change in HDL subfractions and doxorubicin-induced cardiac toxicity.

Protective mechanisms in pulmonary hypertension (PH)

In order to improve the existing therapy offered to patients, a better understanding of the pathophysiology of pulmonary hypertension is needed. Using animal models of pulmonary hypertension, we explore the role of intrinsic cardiac prosurvival pathways in the development of this pathology. We have recently discovered that melatonin, given at nutritional doses may confer preventive and curative cardioprotective benefits against pulmonary hypertension (Maarman et al, B J Pharmacol, 2017).

 

 

Figure legend: Delineation of the signalling components forming part of the Survivor Activating Factor Enhancement (SAFE) cardioprotective pathway.

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