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.
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 the SAFE (Survivor Activating Factor Enhancement) pathway (Lecour, J Mol Cell Cardiol, 2009). Our current research aims to better characterize this novel path which represents great potential in the development of new drug therapies for ischemic heart disease (Hadebe et al, Basic Res Cardiol, 2018).
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 and HIV (see Woudberg et al, J Obes, 2019; Lipids Health Dis, 2018; Hudson et al, Am J Physiol, 2020). Our current research also 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).
Dietary melatonin and pulmonary hypertension
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. Our research also focuses on the finding of safe and inexpensive therapies to limit cardiac damage against the disease (Maarman and Lecour, CVJA, 2021). Our work published recently in Journal of Pineal Research (Maarman et al, 2015), strongly suggests that a chronic treatment of melatonin given as a preventive or curative treatment at a dietary level into drinking water, confers cardioprotection in animals with pulmonary hypertension. The recent acquisition of a new echocardiography machine (Vevo 2100) will assist us to better understand the mechanism in melatonin-induced cardioprotection against this disease which currently lacks of efficient therapy.
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.
The Cape Heart Institute (CHI) is part of the University of Cape Town (UCT) Faculty of Health Sciences.
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UCT Faculty of Health Sciences
Cape Town, South Africa