Grant: Operating Grant

Despite improvements in terms of management and treatment over the past 30 years, cardiovascular diseases still represent the leading cause of death in Western societies. Moreover, a raising number of patients suffer from diabetes, of which 80 percent will die of a heart attack. Accordingly, in light of (i) socioeconomic considerations; (ii) the need for new treatments for these patients; as well as (iii) the need for discovery of biomarkers (molecules that could be measured in blood or urine) to predict the risk of developing heart diseases or diabetes, there has been a major resurgence of interest in the role of nutrients and their assimilation by the body in general, and its implication for the heart in particular. In fact, it is now recognized that the diseased heart is "energy-starved in the midst of plenty", because he is unable to efficiently use blood nutrients or metabolites (sugars and lipids) for the production of energy essential for contraction. For this reason, "metabolic therapies" aiming at enhancing the efficiency of nutrient utilization are currently being considered as alternatives to the currently used treatments. However, the ultimate success of this approach relies in part on a better understanding of the cellular mechanisms governing the utilization of these nutrients by the diseased heart as well as their fate, which include energy production, but also the formation of side-products that can potentially be toxic for the heart. The objective of this research project is to dissect the cellular mechanisms responsible for altered nutrient utilization by the diseased heart using various animal models, including models of diabetes, and pharmacological interventions that specifically target them. Furthermore, we will develop state-of-the-art technologies for screening of new molecules in biological fluids, which could improve our capability to predict disease development in a given individual.