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.
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 (synthetized by our research collaborators in Switzerland), we aim to demonstrate that sphingosine-1 phosphate contributes to the cardioprotective effect of HDL against reperfusion injuries. With the recent acquisition of the Lipoprint System, we are now able to measure different subclasses of HDL and compare the distribution of these subclasses with the functionality of the HDL in different populations with various cardiovascular pathologies .
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. 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.
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Faculty of Health Sciences
University of Cape Town
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Observatory, South Africa