Autophagy, Oxidative Stress and Hippo Signaling in Human Aortic Aneurysm

Primary Outcome Measures:

• Comparison between the levels of Hippo signaling and autophagy markers observed in aortic aneurysms and the levels assessed in the adjacent non-aneurysmatic aortic portions. [ Time Frame: 1 month ]
  Quantification by immunoblot of markers of Hippo signaling (MST1, YAP) and autophagy (LC3, p62, Beclin1, Atg5, Atg7, Ulk1. Adjacent aortic fragments without aneurysm belonging to the same patient will be used as control.
  
  

Secondary Outcome Measures:

• Impact of cardiovascular risk factors on the autophagy levels in aortic samples of patients undergoing surgical procedure of aortic aneurysm removal. [ Time Frame: 1 month ]
  Quantification by immunoblot of markers of autophagy (LC3, p62, Beclin1, Atg5, Atg7, Ulk1) and its statistical correlation with cardiovascular risk factors, such as age, diabetes, obesity, hypercholesterolemia, metabolic syndrome
  
  
• Correlation between levels of autophagy and apoptosis in aneurysmal samples [ Time Frame: 1 month ]
  Quantification by immunoblot of markers of autophagy and apoptosis
  
  
• Correlation between levels of autophagy and endothelial function in patients undergoing surgical procedure of aortic aneurysm removal [ Time Frame: 1 month ]
  flow- mediated dilatation (FMD) in subject underwent surgical procedure of aortic substitution/dissection
  
  
• Correlation between levels of autophagy and the size of aortic aneurysms [ Time Frame: 1 month ]
  Aneurysmal dimension will be evaluated by CT angiography
  
  

Other Outcome Measures:

• Correlation between autophagy, oxidative stress and inflammation [ Time Frame: 1 month ]
  western blot for markers of autophagy, ELISA and HPLC analyses for markers of oxidative stress
  
  
• Correlation between levels of autophagy and the Hippo pathway [ Time Frame: 1 month ]
  western blot for marker of autophagy and the Hippo pathway
  
  

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. We 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.