The major objective of the Cardioprotection Group is the delineation of novel cardioprotective pathways that can be activated to limit cell death in various pathophysiological conditions, such as heart failure, myocardial infarction or diabetes.
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 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.
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 aim to demonstrate that sphingosine-1 phosphate 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 different pathophysiological conditions.
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.