Unit:
Τομέας ΧειρουργικήςLibrary of the School of Health Sciences
Dissertation committee:
Λιακάκος Θεόδωρος-Κων/νος, Καθηγητής, Ιατρική, ΕΚΠΑ
Κυριακοπούλου- Λυμπέρη Μαρία, Καθηγήτρια Ιατρική, ΕΚΠΑ
Κλωνάρης Χρήστος, Καθηγητής, Ιατρική, ΕΚΠΑ
Γεωργόπουλος Σωτήριος, Καθηγητής, Ιατρική, ΕΚΠΑ
Γαζούλης Μαρία, Αναπληρώτρια Καθηγήτρια, Ιατρική, ΕΚΠΑ
Μπακογιάννης Χρήστος, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
Κώτσης Θωμάς, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
Original Title:
Διερεύνηση του ρόλου των microRNAs στη ρύθμιση γονιδίων που εμπλέκονται στην ανάπτυξη ανευρύσματος κοιλιακής αορτής
Translated title:
Investigating the role of microRNAs in genes regulation involved in the development of abdominal aortic aneurysm
Summary:
Objectives: The LRP1 and DAB2IP genes have been suggested as potential candidate genes leading abdominal aortic aneurysm (AAA). The aim of our study was to elucidate whether mir-335-5p and mir-545-3p are regulators of LRP1 expression and mir-363-3p and EZH2 are mediators of DAB2IP, and to investigate the effect of LRP1 expression in other important molecules of AAA pathogenesis, such as MMP2, MMP9 and TSP2.
Materials-Methods: Samples were collected from patients during open surgical AAA repair and adjacent non-aneurysmatic regions were used as controls. Relative mRNA expression levels of of genes and miRNAs LRP1 were measured using rt-real time PCR. Western blot was used to quantify the levels of LRP1, MMP2 and MMP9 protein. A functional study followed, testing the effect of mir-335-5p overexpression on LRP1 expression.
Results: A significant reduction of both LRP1 mRNA and protein level (1.5 fold and 2.76 fold decrease, respectively) was observed in human AAA tissues compared to controls. AAA tissues showed a significant overexpression of both mir-335-5p (~1.49 fold increase) and mir-545-3p (1.36 fold increase). The Pearson correlation showed a limited negative correlation between LRP1 expression levels and both miRNAs. The functional study showed extremely significant decreased expression of LRP1 in cells overexpressing mir-335-5p. The functional study indicated an extremely significant reduced LRP1 mRNA expression in cells overexpressing mir-335- 5p. MMP2 and MMP9 levels were significantly increased in AAA tissues. No significant difference in expression of TSP2 mRNA was observed. DAB2IP was significantly overexpressed (2.29 times) in AAA tissues, while EZH2 and mir-363-3p were found to be decreased (3.28 and 3.62 times respectively). A limited negative association was found between DAB2IP and EZH2 expression and between DAB2IP and mir-363-3p.
Conclusions: In our study, LRP1 reduction in AAA tissues was confirmed and attributed to mediated regulation via mir-335-5p. It is suggested that LRP1 has a direct effect on the regulatory activity of MMPs. We recommend 2 potential mediators, EZH2 and mir-363-3p of DAB2IP expression in AAA tissues. The study of other molecules in the regulation of these genes will elucidate the molecular pathway of the disease.
Main subject category:
Health Sciences
Keywords:
Abdominal aortic aneurysm, DAB2IP, LRP1, MicroRNAs, Gene regulation
Number of references:
317
