Grant: Team Grant: Transnational Cardiovascular Research Projects

Heart failure (HF) is a complex disease resulting from the incapacity of the heart to effectively contract and unfortunately this pathology is a major leading cause of mortality. There is therefore an urging need to find new therapeutic options to slow down the course of this pathology and reduce the mortality rate. The failing heart might be defined as "an engine out of fuel" where the power station of the cell, named mitochondria, is dysfunctional and where the fuel, namely nutrients, replenishing this power station is not correctly used. Moreover, the calcium, important for this contractility process, is also misused in the failing heart, which again affects heart function. All these disregulated events are closely linked to disease progression. In this regard, efforts are undertaken to fix this power station in HF and propose as a metabolic therapy of HF. We are building on complementarity expertise of all members of the Consortium to validate the relevance of using a metabolic therapy using a cocktail of B vitamins, either alone or in combination with current drugs used to treat HF, first in experimental animal models of HF as a proof-of concept. To achieve our aims, the efficiency of such treatment will be evaluated with animal survival rate, and as secondary outcomes we will examine i) in vivo and ex vivo heart function, ii) mitochondrial function, iii) how nutrients needed for an optimal function of mitochondria are used, in other terms metabolized, by the heart, and iv) how the calcium used to promote contractility is processed by cardiac cells. Through this Consortium, we are confident to validate and propose a relevant metabolic therapy for HF that will correct both the energetic deficiency and the defect in contractility of the heart. This will be ultimately of significant clinical relevance to offer alternative or add-on therapy improving the survival of HF patients.