*4.2. Oleuropein and Cardioprotection*

Miceli et al. [107] studied the e ffect of OleA as an autophagy enhancer in a cardiomyocyte model, characterized by autophagy dysfunction induced by oxidative stress due to a monoamine oxidase-A (MAO-A) overexpression. MAO-A is an isoform of FAD-dependent enzymes, that catalyzes oxidative deamination of catecholamines and serotonin in the heart, producing the corresponding aldehyde, H2O2, and ammonia. Previous studies have reported that MAO-A expression and activity increased in chronic cardiac diseases [108–111]. They found that OleA conferred cardioprotection, not simply by its antioxidant action, but through restoration of defective autophagic flux autophagy, reflected by auto-phagolysosome formation, measured by p62 and cathepsin-B levels increase, and the transcriptional factor EB (TFEB) activation and translocation to the nucleus. Translocation of TFEB to the nucleus modulated the transcription of autophagy genes prevented by MAO-A activation, reducing its transcriptional activity. They demonstrated that transcriptional regulation of autophagy by OleA was correlated with a significant cell death decrease, and to mitochondrial functionality recovery. These improvements disappeared after TFEB silencing, leading to the hypothesis that TFEB activaction was crucial for the protective effects of OleA against MAO-A-induced autophagy dysfunction. In addition, TFEB translocation and autophagy recovery induced by OleA did not affect ROS status in cardiomyocytes, further highlighting its peculiarity as an autophagy inducer.
