CardioBDP

01.02.2014 to 31.01.2017

Cardiovascular diseases (CVD) are a group of disorders affecting the heart and blood vessels. It has been established that CVD constitute a major health problem since globally, about 30% of deaths are related to CVD and since their incidence increase dramatically with the ageing of population. Moreover, diet, one of the most important lifestyle risk factors, can strongly influence the progression of CVD and may constitute a promising prophylaxis. Recently, a link between CVD, metabolism, mitochondria and diet has been evidenced. This link might involve a crosstalk between mitochondria functions (e.g. biogenesis, bioenergetics, permeability transition), autophagy and cell death and would be regulated at the cellular level by various classes of sensors such as proteins as well as second messengers such as nitric oxide (NO) or cyclic nucleotides. Thus, mitochondria appear as essential players in promoting diet-induced cytoprotection although more investigations are needed to understand how these organelles control cell metabolism, redox steady-state and cell death in the heart. Academic French and Portuguese partners will conjugate their multidisciplinary expertise in the fields of Nutrition, Cell Biology, Biochemistry and Cardiac Pathophysiology to identify novel cardioprotective agents from original blackberries preparations, namely blackberries-derived polyphenols (BDP). BDP cellular and subcellular mechanisms of protection will be characterized in vitro by using primary cell cultures, cell lines and isolated mitochondria and in vivo by using preclinical models of CVD. This proposal will address three major areas of investigation outlined in the following objectives (1) the study the cytoprotective effects of BDP on preserving mitochondrial functions, stimulating autophagy and inhibiting cell death in primary cardiomyocytes and cell lines; (2) the role of phosphorylation and cyclic nucleotides on the regulation of mitochondrial functions by BDP, and (3) the evaluation of the cardioprotective potential of BDP in two validated rodent models of hypertension and catecholamine-induced cardiotoxicity.

This proposal will offer scientific knowledge easily transferable to humans concerning the bioefficacy of berry polyphenols in cardioprotection and will additionally envisage the support of fresh berries as a valuable nutraceutical product with beneficial effects for consumer’s health. Finally, in addition to contribute to scientific excellence and significant progress towards the state of the art of cytoprotection, we anticipate the possibility to patent innovative preparations and their potential use in cardioprotection, notably in the current context of ageing population in Europe.

The ultimate outcome of CardioBDP is the development of a novel polyphenol-based long-term care strategy against CVD, which are often associated with oxidative stress and ageing. Our hypothesis is groundbreaking and will disclose the mode of action by which berries polyphenols can be cardioprotective and indirectly anti-oxidant via modulation of mitochondrial functions and cell metabolism. A cost effective therapeutic strategy, such as a nutraceutical contributing to increasing the number of healthy life years by delaying the cardiovascular health problems and therefore increasing the quality of life for the citizens, will represent a significant social and economic impact. This is a very important issue in our ageing European population with increased incidence of CV-related diseases and the proposal is aligned with the main goal of European Innovation Partnership to foster “active and healthy ageing”.

BUDGET: €180 000

PRINCIPAL CONTRACTOR:

• Instituto de Biologia Experimental e Tecnológica (iBET)

PARTICIPATING INSTITUTIONS:

• INSERM U769 Faculdade de Chatenay-Malabry (INSERM U769) Paris, France
• Centro de Estudos de Doenças Crónicas (CEDOC) da Faculdade de Ciências Médicas (FCM-UNL)

COLLABORATIONS: Dr. Derek Stewart, from James Hutton Institute (JHI)