Autophagy, Oxidative Stress and Hippo Signaling in Human Aortic Aneurysm
Condition: Aortic Aneurysm
MeSH terms: Aneurysm; Aortic Aneurysm
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Subjects affected by abdominal aortic aneurysms undergoing aortic surgical procedures
      
Biospecimen description: 
      Aortic aneurysm
    
Keywords: aortic aneurysm; autophagy; oxidative stress; Hippo pathway