Disturbed P53-MDM2 Feedback Loop Contributes to Thoracic Aortic Dissection Formation and May be a Result of TRIM25 Overexpression.
Ann Vasc Surg
; 40: 243-251, 2017 Apr.
Article
in En
| MEDLINE
| ID: mdl-27903487
ABSTRACT
BACKGROUND:
The development of thoracic aortic dissection (TAD) is attributed to a broad range of degenerative, genetic, structural, oxidative, apoptotic, and acquired disease states. In this study, we examined the role of the disturbed p53-MDM2 (murine double minute 2) feedback loop in the formation of TAD, and one of a potential feedback loop regulator, TRIM25 (tripartite motif protein-25).METHODS:
Surgical specimens of the aorta from TAD patients (n = 10) and controls (n = 10) were tested for α-smooth muscle actin (α-SMA), p53, MDM2, and TRIM25 by western blot, immunohistochemical staining, and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), respectively.RESULTS:
When compared with controls, western blot shows that the protein levels of p53, MDM2, and TRIM25 were increased significantly in the aortic media of TAD patients. qRT-PCR further verified that the mRNA expression of MDM2 and TRIM25 was also increased 6- and 4-folds, respectively, in the TAD media of the aortic wall. Immunohistochemistry results showed significantly decreased staining of α-SMA, smooth muscle cells, and more collagen deposition in the media of the aortic wall from patients with TAD.CONCLUSION:
This study provided a new insight into the disturbed p53-MDM2 feedback loop in the pathogenesis of TAD, and this may be because of the TRIM25 overexpression.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aorta, Thoracic
/
Transcription Factors
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Tumor Suppressor Protein p53
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Aortic Aneurysm, Thoracic
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Ubiquitin-Protein Ligases
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Proto-Oncogene Proteins c-mdm2
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Tripartite Motif Proteins
/
Aortic Dissection
Type of study:
Observational_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Ann Vasc Surg
Journal subject:
ANGIOLOGIA
Year:
2017
Document type:
Article
Publication country:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
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PAISES BAJOS
/
THE NETHERLANDS