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Tytuł: MicroRNA as potential biomarker of abdominal aortic aneurysms
Abstrakt:
An aortic aneurysm is a localized, abnormal dilatation of the lumen of the aorta. The affected vessel has been shown to have histological abnormalities and a wall susceptible to dissection or rupture. Risk factors include smoking, hypertension, male sex and advanced age, but the unclear pathogenesis of the disease has prevented the introduction of effective conservative treatment. A positive family history is also associated with a significantly higher risk of the disease, but a consistent inheritance model is still not in place. This suggests the involvement of epigenetic processes in its pathogenesis, which in turn allows attempts to use molecules that modify genetic expression as potential biomarkers to diagnose or monitor disease progression. Indeed, the lack of specific biomarkers makes it difficult to choose the right time for elective surgery. The present study therefore sought to evaluate noncoding RNAs in the context of abdominal aortic aneurysms, both in terms of their association with disease pathogenesis and their potential use as biomarkers. The work was preceded by a preliminary study in which the profile of microRNAs in the serum of patients with abdominal aortic aneurysms was determined in comparison to controls. A pool of 10 molecules was selected that best differentiated the study group from the control group. The levels of the selected molecules were measured ; as the number of patients increased, and a subset of molecules (miR-191, miR-126 and miR-21-5p) most likely to be involved in the pathogenesis of the disease were identified and their effect on the transcriptome was experimentally studied using an in vitro model of cells with an endothelial phenotype. The circular part of this transcriptome was also taken into account and, under these model conditions, molecules with the potential to act as biomarkers were selected among the circular RNAs. The study showed that miR-191 levels differed significantly between the study and control groups. This molecule exerts pleiotropic effects on the transcriptome of endothelial cells, leading to changes in the expression of more than 1,000 genes, and some of the observed changes can be linked to disorders described in the pathogenesis of abdominal aortic aneurysms. In addition to transcripts for protein-coding genes, numerous circular RNAs are present in endothelial cells. Transfected exogenous microRNAs also influence this part of the transcriptome, supporting the hypothesis of a network of interdependencies between microRNAs, circular RNAs and transcripts of protein-coding genes.
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Rada Dyscypliny Nauki medyczne
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Data ostatniej modyfikacji:
8 paź 2024
Data dodania obiektu:
22 maj 2024
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http://dl.cm-uj.krakow.pl:8080/publication/5114
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| Nazwa wydania | Data |
|---|---|
| ZB-140335 | 8 paź 2024 |
Obiekty
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