Autophagy, Oxidative Stress and Hippo Signaling in Human Aortic Aneurysm

NCT03211000 | Completed

• 1 other identifier: 6-2017
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Aortic Aneurysm

Keywords

aortic aneurysm; autophagy; oxidative stress; Hippo pathway

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  1 month

Secondary Outcomes (4)

• Impact of cardiovascular risk factors on the autophagy levels in aortic samples of patients undergoing surgical procedure of aortic aneurysm removal.

  1 month

• Correlation between levels of autophagy and apoptosis in aneurysmal samples

  1 month

• Correlation between levels of autophagy and endothelial function in patients undergoing surgical procedure of aortic aneurysm removal

  1 month

• Correlation between levels of autophagy and the size of aortic aneurysms

  1 month

Other Outcomes (2)

• Correlation between autophagy, oxidative stress and inflammation

  1 month

• Correlation between levels of autophagy and the Hippo pathway

  1 month

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Subjects affected by abdominal aortic aneurysms undergoing aortic surgical procedures

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Neuromed IRCCS: lead

Study Sites (1)

IRCCS Neuromed

Pozzilli, Isernia, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

Aortic aneurysm

MeSH Terms

Conditions

Aortic Aneurysm

Condition Hierarchy (Ancestors)

Aneurysm; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases

Study Officials

• Giacomo Frati, MD

  IRCCS Neuromed

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: July 5, 2017
• First Posted: July 7, 2017
• Study Start: June 1, 2017
• Primary Completion: October 31, 2017
• Study Completion: November 1, 2017
• Last Updated: April 11, 2022

Record last verified: 2022-04

Locations

IT (1)