Unit:
Τομέας ΧειρουργικήςLibrary of the School of Health Sciences
Author:
Τούμπουλης Ιωάννης
Dissertation committee:
Ιωάννης Ρίζος (Αναπληρωτής Καθηγητής, Επιβλέπων), Κωνσταντίνος Αναγνωστόπουλος (Ομότιμος Καθηγητής, Μέλος), Νικόλαος Ανάγνου (Καθηγητής, Μέλος)
Original Title:
Αλλαγές στην έκφραση τύπων κολλαγόνου που σχηματίζουν ινίδια στα ανευρύσματα της ανιούσας θωρακικής αορτής
Summary:
Background: Human ascending thoracic aortic aneurysms are life threatening and
constitute a leading cause of mortality in the elderly. The molecular
mechanisms leading to ascending thoracic aortic aneurysms remain unknown. In
the present study was evaluated the hypothesis that alterations in expression
levels of specific fibrillar collagens occur during the aneurysmal process.
Materials and methods: Surgical samples from human ascending thoracic aortas
from patients with degenerative aneurysms were collected and were divided by
aneurysm diameter to small, medium and large aneurysms and were compared with
normal diameter ascending thoracic aortas. In addition detailed proteomic
analysis was performed in order to determine biomarkers in the peripheral blood
using qRT-PCR that will allow the identification of ascending thoracic aortic
aneurysms prior to acute aortic dissection or aortic rupture.
Results: Histology, immunofluorescence, immunohistochemistry and transmission
electron microscopy demonstrated greater fragmentation and disorganization of
extracellular matrix constituents in ascending thoracic aortic aneurysms as
compared with normal diameter aortas with an increase in collagen XI-α1 within
regions of cystic medial degenerative lesions. Transmission electron microscopy
showed a statistically significant reduction of 25% (P<0.001) in the diameter
of collagen fibrils in ascending thoracic aortic aneurysms. Analysis with
qRT-PCR showed collagens V and XI-α1 were significantly and linearly increased
in ascending thoracic aortic aneurysms compared to normal diameter aortas
(P<0.001). Western blot analysis showed collagen type I and III were
significantly decreased and collagens XI-α1 and V were significantly increased
and were linearly correlated with the size of the aneurysm (P<0.001 for all).
Five biomarkers were identified as being suitable for detection and
identification of ascending thoracic aortic aneurysms using qRT-PCR analysis of
peripheral blood. Analysis of 41 samples (19 small, 13 medium and 9 large
ascending thoracic aortic aneurysms) demonstrated that the overexpression of 3
of 5 biomarkers provides 100% specificity and 79% sensitivity allowing
identification of ascending thoracic aortic aneurysms 4.0cm or greater in males
and females.
Conclusions: Increased collagen ΧΙ-α1 and collagen V mRNA and protein levels
are linearly correlated with the size of the aneurysm of the ascending thoracic
aorta and provide for the first time a potential mechanism for the generation
and progression of ascending thoracic aortic aneurysms. The ability to provide
rapid evaluation of potential ascending thoracic aortic aneurysms in patients
using peripheral blood strengthens the armamentarium currently available to
clinicians and surgeons.
Keywords:
Ascending thoracic aortic aneurysm, Collagen, Molecular biology, Molecular mechanism, Biomarkers
Number of references:
163
