Background: Abdominal aortic aneurysms (AAA) are relatively frequent in elderly population, and their ruptures are related with high mortality rate. There are no actually used laboratory markers predicting the AAA development, course, and rupture. MicroRNAs are small noncoding molecules involved in posttranscriptional gene expression regulation, influencing processes on cell and tissue levels, and are actually in focus due to their potential to become diagnostic or prognostic markers in various diseases. Methods: Tissue samples of AAA patients and healthy controls were collected, from which miRNA was isolated. Microarray including the complete panel of 2549 miRNAs was used to find expression miRNA profiles that were analysed in three subgroups: small (N = 10) and large (N = 6) aneurysms and healthy controls (N = 5). Fold changes between expression in aneurysms and normal tissue were calculated including corresponding p values, adjusted to multiple comparisons. Results: Six miRNAs were found to be significantly dysregulated in small aneurysms (miR-7158-5p, miR-658, miR-517-5p, miR-122-5p, miR-326, and miR-3180) and 162 in large aneurysms, in comparison with the healthy control. Ten miRNAs in large aneurysms with more than two-fold significant change in expression were identified: miR-23a-3p, miR-24-3p, miR-27a-3p, miR-27b-3p, miR-30d-5p, miR-193a-3p, miR-203a-3p, miR-365a-3p, miR-4291, and miR-3663-3p and all, but the last one was downregulated in aneurysmal walls. Conclusion: We confirmed some previously identified miRNAs (miR-23/27/24 family, miR-193a, and miR-30) as associated with AAA pathogenesis. We have found other, yet in AAA unidentified miRNAs (miR-203a, miR-3663, miR-365a, and miR-4291) for further analyses, to investigate more closely their possible role in pathogenesis of aneurysms. If their role in AAA development is proved significant in future, they can become potential markers or treatment targets.
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Background: Atherosclerosis and bone metabolism share similar molecular and cellular mechanisms. This study aims to evaluate (1) serum concentration of osteogenesis/osteolysis factors panel (Dickkopf-related protein 1 (DKK-1), TNF-α, N-terminal atrial natriuretic peptide (NT-proANP), thrombospondin-2 (TSP-2), osteoprotegerin (OPG), osteocalcin (OCN), osteopontin (OPN), fibroblast growth factor 23 (FGF-23), soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), proprotein convertase subtilisin/kexin type 9 (PCSK9)), (2) serum expression levels of micro-RNA- (miR-) 24-1 and miR-6802, and (3) assess their correlation with myocardial injury and LV remodeling and function in the acute phase of STEMI and after 3 months. Methods: Study enrolled 25 STEMI patients (mean age 55.4 ± 8.96 years). Blood samples were collected 4 days and 3 months after myocardial infarction. Serum concentrations of osteogenesis/osteolysis factors were measured using the Luminex assay. Analysis of miR-24-1, and miR-6802 expression was performed with qPCR. LV function and remodeling were assessed by MRI during index hospitalization and 3 months later. Results: There were no significant differences in serum levels of osteogenesis/osteolysis factors and expression of miR-24-1 and miR-6802 between the acute phase and 3-month follow-up. The levels were similar in patients with at least ≥5% improvement of LVEF (n = 10) and those without improvement. There was a negative correlation between the OPG serum level and LVEF during the acute phase of myocardial infarction. Conclusions: In STEMI patients, serum concentrations of osteogenesis/osteolysis factors, as well as miR-24-1 and miR-6802 expression, do not change significantly within the 3-month follow-up and are not correlated with LV remodeling and function.
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- časopisecké články MeSH
