Autophagy, Oxidative Stress and Hippo Signaling in Human Aortic Aneurysm

The molecular mechanisms contributing to the development of aortic aneurysmal disease are poorly characterized making actual therapies not sufficient. Autophagy is an intracellular mechanism that removes dysfunctional organelles and unfolded proteins, thereby maintaining cellular homeostasis. Activation of autophagy was shown to limit cardiac damage during stress. Accordingly, autophagy was found to be inhibited in the heart in animal models of metabolic syndrome, diabetes, obesity and aging thereby contributing to the development of cardiac derangements associated with these conditions. However, it remains to fully dissect the association between autophagy and structural alterations of the aortic wall and endothelial dysfunction in humans. In this study the correlation between levels of autophagy and the development of human aortic aneurysm will be assessed in patients subjected to surgical interventions for aortic pathologies. The association of Hippo signaling activation with the formation of aortic disease will also be evaluated, since previous work demonstrated that the Hippo pathway negatively regulates autophagy and promotes the development of cellular abnormalities. The results of this study may provide new insights into the mechanisms underlying the development of aortic disease.