Synergistic beneficial effects of natural activators of autophagy on endothelial cells and platelets.

BACKGROUND AND PURPOSE Oxidative stress and insufficient autophagy activity are associated with inflammatory processes and are common features of many cardiovascular diseases (CVD). We investigated if a combination of natural activators of autophagy is able to modulate oxidative stress, platelet aggregation and endothelial cell survival and function in response to stress. EXPERIMENTAL APPROACH Ex vivo platelet aggregation and activation, H2 O2 production and autophagy were measured in platelets of subjects at high cardiovascular risk, including smokers, patients with metabolic syndrome (MS) and patients with atrial fibrillation (AF). In vitro, the effects of a mixture of natural pro-autophagy molecules and antioxidants on platelets and HUVECs were evaluated. KEY RESULT Autophagy appeared to be inhibited, whereas aggregation was increased in platelets from AF and MS patients and in smokers, as compared to healthy subjects. Treatment of platelets isolated from these patients with 2 different mixtures of catechin, epicatechin, trehalose and spermidine significantly reduced platelet activation and oxidative stress, whereas they increased autophagy in a synergistic manner with respect to the effect of each single molecule alone. Similarly, treatment of HUVECs with a combination of these natural compounds exerted synergic beneficial effects and increased endothelial cell survival, NO bioavailability and angiogenesis in response to stress in a potentiated manner. CONCLUSION AND IMPLICATIONS A combination of natural activators of autophagy could synergistically inhibit platelet activity and oxidative stress and improve endothelial cell survival and function in a potentiated manner representing a useful strategy to reduce the impact of risk factors on CVD occurrence.