0281 : Protection of berries polyphenols in response to cardiac stress might involve other mechanisms than a mitochondrial direct action

Abstract

Cardiovascular diseases (CVD) are the leading cause of death in the developing world. Epidemiological studies have shown a consistent relationship between the consumption of fruits and vegetables and a reduced risk of CVD susceptibility. Among mechanisms underlying the decline of cardiac pump function in heart failure (HF), chronic elevation of cAMP, protein post-translational modifications and mitochondrial dysfunction emerge as major contributing factors. Thus, (i) modulation of the cAMP-hydrolyzing phosphodiesterase (PDE) activity and (ii) maintaining a proper function of mitochondria to ensure cellular process metabolite synthesis, calcium homeostasis and cell death, can have a positive effect on the heart. The aim was to evaluate the contribution of polyphenols on the prevention of mitochondrial permeability transition, a process which can lead to cell death and on the modulation of cardiac PDE activity and cAMP levels ex vivo. Wistar rats were divided into 2 groups. In a first group, cardiac tissues were collected to isolate mitochondria and measure mitochondria transmembrane potential and matrix swelling induced by calcium (Ca2+) and tert- Butyl hydroperoxide (t-BHP). In the second group, hearts were excised and lysed to measure PDE activity. Large range of concentrations of polyphenols showed no mitochondrial pore transition protection in response to 50μMCa2+ mitochondria and to oxidative stress induced by tert-Butyl hydroperoxide (t-BHP). Experiments on cardiac PDEs are on-going and results will be compared to resveratrol, which has been shown to inhibit PDE 1, 3, and 4 in the heart. These results suggest that if these polyphenols metabolites have a cardioprotective effect in vivo, it might be rather mediated by an indirect effect on cardiac mitochondria such as modulation of PDE activity or others cellular targets. Further investigations will be performed to fully elucidate the targets of polyphenols effects. Funding (ANR and FCT-ANR) The author hereby declares no conflict of interest