Résumé
Cardioprotective effects of long-chain polyunsaturated fatty acids of the n-3 series (PUFAs) have been demonstrated and represent a novel approach to prevent myocardial infarctions or its consequences. Due to the abundance of double bonds, the main n-3 PUFAs; docosahexaenoic acid (C22: 6 n-3, DHA) are very sensitive to free radical oxidation and can undergo non-enzymatic spontaneous peroxidation under oxidative stress conditions as it occurs in ischemia/reperfusion. In this context, a lot of oxygenated metabolites of PUFAs-like neuroprostanes (NeuroPs) are produced and used as oxidative stress biomarkers but their activities were not determined.
We investigated if the pericardial delivery of NeuroPs, protects the myocardium from ischemic damages during and following an ischemia/reperfusion (IR) episode in rats.
Cardiac functions, infarct size and arrhythmias were studied and we observed that NeuroPs afford some cardioprotective effect during or after myocardial infarction. Indeed, compared with controls, NeuroPs-treated animals have significantly decreased infarct size (−28%) determined at the end of reperfusion and reduced ventricular arrhythmia score during reperfusion (−38%). Mechanistically, NeuroPs regulates calcium levels by stabilizing RyR2 activity (Roy et al., 2015), which can explain arrhythmias prevention during IR. Also, our results demonstrated an increase of membrane potential (ΔΨm) by the application of NeuroPs. This effect was not due to an augmentation of mitochondrial respiratory chain activity but by the effect leading to the diminution of protons leak. Swelling in response to Ca2+ was prevented by NeuroP, indicating a decrease MPTP opening, which can be explain prevention of cell death during IR.
These results suggest a novel pharmacological pathway of n-3 PUFAs and suggest that their well-known cardioprotective effects are mediated by their oxygenated metabolites such as NeuroPs.