Autophagy, Oxidative Stress and Hippo Signaling in Human Aortic Aneurysm

Autophagy may represent a new potential therapeutic target for the prevention and the treatment of aortic pathologies. It is a cellular self- digestion mechanism that prevents the accumulation of senescent organelles and damaged proteins. Autophagy plays a pivotal role in the regulation of cellular homeostasis and promotes the cellular response to stress. However, further investigations are needed to establish how autophagy is influenced by cardiovascular risk factors, as well as by pharmacological therapy. Moreover, it is still unclear in humans the association between autophagy and structural and functional alterations of aortic wall, as well as its association with endothelial dysfunction, especially in subjects affected by aortic pathologies. Furthermore, no data are available on the correlation between autophagy and the prognosis of patients who underwent cardio-surgical procedures for aortic pathologies. In this study, autophagy levels will be evaluated in human aortic aneurysm samples obtained from patients enrolled for a surgical aorta procedures. Autophagy markers in each aneurysm sample will be compared to those observed in the non-aneurysmatic aortic portion adjacent to the aneurysmatic tract obtained from the same patient. Levels of autophagy will also be correlated with markers of apoptosis and oxidative stress in both the aneurysmatic and non-aneurysmatic aortic parts. The involvement of the Hippo signaling pathway and inflammation in control and aneurysm samples will also be investigated. The investigators expect that autophagy levels will be lower in aneurysm samples with respect to non-aneurysmatic adjacent aortic portions. They will also be inversely correlated with aneurysm dimension. In contrast, the Hippo pathway will be activated in aortic aneurysms. Autophagy and Hippo signaling markers will also be correlated with markers of apoptosis and oxidative stress in aortic samples. In conclusion, the results of this study may underline the vascular role of autophagy and Hippo signaling and their involvement in the development of aortic diseases.

Inclusion criteria

• Eligible subjects undergoing aortic surgical procedures
• Ejection fraction (FE) > 30%
• Acceptance and signature of the informed consent

Exclusion criteria

• Acute myocardial infarction in the last 6 months
• Chronic and acute Inflammatory diseases
• Immunological and rheumatic diseases
• Pre-existing or ongoing neoplasms
• infectious diseases
• Treatment with pharmacological therapies able to modulate autophagy, i. e. rapamycin and derivative compounds (rapalogues))
• Antioxidant therapies in the last three months
• Patients with surgical technical complications