Balkan Journal of Medical Genetics

A PRELIMINARY microRNA ANALYSIS OF NON SYNDROMIC THORACIC AORTIC ANEURYSMS
Patuzzo C1,*, Pasquali A1, Malerba G1, Trabetti E1, Pignatti PF1, Tessari M2, Faggian G2
*Corresponding Author: Dr. Cristina Patuzzo, Department of Life and Reproduction Sciences, University of Verona, Strada Le Grazie 8, 37134,Verona, Italy; Tel.: +39-45-802-7207; Fax: +39-45-802-7180; E-mail: cristina.patuzzo@univr.it
page: 51

DISCUSSION

In this study, RNA pools obtained from ascending thoracic aortic wall fragments of patients affected by TAA were competitively hybridized with control pools on microarrays spotted with oligonucleotides putatively recognizing 728 miRNAs. Ninety-nine miRNAs were differentially expressed. The miRNA sequences listed were matched to gene sequences and linked to annotated pathways of gene expression. The most enriched pathways, which included a high number of putative target genes of differentially expressed miRNAs, were focal adhesion and adherens junction. The most interesting result concerned the 11 upregulated miRNAs, both in male and female TAAs, which putatively matched 61 genes related to the adhesion processes. This indicates a significant modulation, i.e., repression, of the focal adhesion pathway. The adherens junction pathway, on the basis of the putative targeting by miRNAs, resulted as repressed and stimulated in 26 and 15 genes, respectively. These opposite signals could be a manifestation of the cellular cohesion impairment and of the attempt to reconstitute the integrity of the aortic wall during the development of TAA. No sex differences were observed in the present study, as miRNAs differentially expressed in males versus females targeted genes belonging to the same general pathways. Some of the differentially expressed miRNAs identified in this study are in agreement with the literature, as reported below. Down-Regulated microRNAs. Phenotypic abnormalities of vascular smooth muscle cells (VSMCs) and cardiomyocytes have been observed in MIR-133 knockout mice [15]. MIR-145 is decreased in aortas from patients with an aneurysm and was suggested as a potential biomarker for vascular diseases [16]. Up-Regulated microRNAs. MIR-126, the most up-regulated miRNA in this study, has been implicated in the maintenance of vascular integrity [17] and in vascular cell adhesion molecule expression [18]. MIR-29B-mediated down-regulation of ECM proteins predisposes the aorta to the formation of aneurysms [19]. MIR-21 has been investigated extensively in various tissues and it has been found to promote vascular smooth muscle cell (VSMC) proliferation [16]. Knockdown of MIR- 221 and MIR-222 by antisense oligonucleotide miRNA depletion has been foun to reduce VSMCs proliferation in response to vascular injury, and both miRNAs are strongly elevated in vivo in VSMCs following vessel injury [16]. MIR-146, MIR-24 and MIR-26 have been implicated in VSMCs proliferation and contraction [16]. MIR-15A, MIR-16, MIR- 16-1, MIR-16-2, and MIR-195 belong to a family of miRNAs (the miR-15 family) consistently found to be up-regulated in cardiovascular diseases [5]. In conclusion, and in concordance with other investigators [20], our study indicates that the weakness of the ascending aortic tissue in TAA is linked with a perturbation of cell adhesion and cell interaction gene expression pathways. MicroRNAs probably act as regulators, possibly driving, or at least influencing, the development of the disease.

Number 27 VOL. 27 (2), 2024	Number 27 VOL. 27 (1), 2024
Number 26 Number 26 VOL. 26(2), 2023 All in one	Number 26 VOL. 26(2), 2023
Number 26 VOL. 26, 2023 Supplement	Number 26 VOL. 26(1), 2023
Number 25 VOL. 25(2), 2022	Number 25 VOL. 25 (1), 2022
Number 24 VOL. 24(2), 2021	Number 24 VOL. 24(1), 2021
Number 23 VOL. 23(2), 2020	Number 22 VOL. 22(2), 2019
Number 22 VOL. 22(1), 2019	Number 22 VOL. 22, 2019 Supplement
Number 21 VOL. 21(2), 2018	Number 21 VOL. 21 (1), 2018
Number 21 VOL. 21, 2018 Supplement	Number 20 VOL. 20 (2), 2017
Number 20 VOL. 20 (1), 2017	Number 19 VOL. 19 (2), 2016
Number 19 VOL. 19 (1), 2016	Number 18 VOL. 18 (2), 2015
Number 18 VOL. 18 (1), 2015	Number 17 VOL. 17 (2), 2014
Number 17 VOL. 17 (1), 2014	Number 16 VOL. 16 (2), 2013
Number 16 VOL. 16 (1), 2013	Number 15 VOL. 15 (2), 2012
Number 15 VOL. 15, 2012 Supplement	Number 15 Vol. 15 (1), 2012
Number 14 14 - Vol. 14 (2), 2011	Number 14 The 9th Balkan Congress of Medical Genetics
Number 14 14 - Vol. 14 (1), 2011	Number 13 Vol. 13 (2), 2010
Number 13 Vol.13 (1), 2010	Number 12 Vol.12 (2), 2009
Number 12 Vol.12 (1), 2009	Number 11 Vol.11 (2),2008
Number 11 Vol.11 (1),2008	Number 10 Vol.10 (2), 2007
Number 10 10 (1),2007	Number 9 1&2, 2006
Number 9 3&4, 2006	Number 8 1&2, 2005
Number 8 3&4, 2004	Number 7 1&2, 2004
Number 6 3&4, 2003	Number 6 1&2, 2003
Number 5 3&4, 2002	Number 5 1&2, 2002
Number 4 Vol.3 (4), 2000	Number 4 Vol.2 (4), 1999
Number 4 Vol.1 (4), 1998	Number 4 3&4, 2001
Number 4 1&2, 2001	Number 3 Vol.3 (3), 2000
Number 3 Vol.2 (3), 1999	Number 3 Vol.1 (3), 1998
Number 2 Vol.3(2), 2000	Number 2 Vol.1 (2), 1998
Number 2 Vol.2 (2), 1999	Number 1 Vol.3 (1), 2000
Number 1 Vol.2 (1), 1999	Number 1 Vol.1 (1), 1998

About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact