Evaluation of microribonucleic acids as potential biomarkers in the bicuspid aortic valve-associated aortopathy†

Girdauskas, Evaldas; Petersen, Johannes; Neumann, Niklas; Gross, T. M. Sequeira; Naito, Shokichi; Hillebrand, Mathias; Reichenspurner, Hermann; Blankenberg, Stefan; Zeller, Tanja

doi:10.1093/icvts/ivy033

Cited by 17 publications

(14 citation statements)

References 25 publications

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“…Nevertheless, we found relevant differences in the microRNA expression patterns which might be valuable, considering even the limitations of our preliminary study. Inverse linear correlation between proximal aortic diameters and the CT values of circulating microRNAs have been described previously and linked to specific cellular pathways [9,21]. In accordance to these studies, we were able to confirm an inverse linear correlation between maximum aortic diameters and the values of circulating microRNA-17 and microRNA-20a in the pooled study population.…”

Section: Discussionsupporting

confidence: 89%

“…Young and predominantly male patients presenting with BAV regurgitation and concomitant aortic root dilatation demonstrate an increased prevalence of genetic abnormalities (i.e., TGFBR2, FBN1, NOTCH1, and SMAD2) [19,20]. As reported previously, such patients potentially have the most malignant aortopathy and, therefore, may present with the most extensive derangements in the microRNA expression [21]. To test this hypothesis, we examined the levels of circulating microRNA in the BAV root phenotype patients (i.e., BAV-AR subgroup) and compared them with other valvulo-aortic phenotypes of aortic valve lesions (i.e., BAV-AS and TAV-AS subgroups).…”

Section: Discussionmentioning

confidence: 60%

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Expression Patterns of Circulating MicroRNAs in the Risk Stratification of Bicuspid Aortopathy

Girdauskas

Neumann²,

Petersen

et al. 2020

JCM

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Objective: Aortic size-based criteria are of limited value in the prediction of aortic events, while most aortic events occur in patients with proximal aortic diameters < 50 mm. Serological biomarkers and especially circulating microRNAs (miRNAs) have been proposed as an elegant tool to improve risk stratification in patients with different aortopathies. Therefore, we aimed to evaluate the levels of circulating miRNAs in a surgical cohort of patients presenting with bicuspid aortic valve disease and distinct valvulo-aortic phenotypes. Methods: We prospectively examined a consecutive cohort of 145 patients referred for aortic valve surgery: (1) Sixty three patients (mean age 47 ± 11 years, 92% male) with bicuspid aortic valve regurgitation and root dilatation (BAV-AR), (2) thirty two patients (mean age 59 ± 11 years, 73% male) with bicuspid aortic valve stenosis (BAV-AS), and (3) fifty patients (mean age 56 ± 14 years, 55% male) with tricuspid aortic valve stenosis and normal aortic root diameters (TAV-AS) who underwent aortic valve+/-proximal aortic surgery at a single institution. MicroRNAs analysis included 11 miRNAs, all published previously in association with aortopathies. Endpoints of our study were (1) correlation between circulating miRNAs and aortic diameter and (2) comparison of circulating miRNAs in distinct valvulo-aortic phenotypes. Results: We found a significant inverse linear correlation between circulating miRNAs levels and proximal aortic diameter in the whole study cohort. The strongest correlation was found for miR-17 (r = −0.42, p < 0.001), miR-20a (r = −0.37, p < 0.001), and miR-106a (r = −0.32, p < 0.001). All miRNAs were significantly downregulated in BAV vs. TAV with normal aortic root dimensions Conclusions: Our data demonstrate a significant inverse correlation between circulating miRNAs levels and the maximal aortic diameter in BAV aortopathy. When comparing miRNAs expression patterns in BAV vs. TAV patients with normal aortic root dimensions, BAV patients showed significant downregulation of analyzed miRNAs as compared to their TAV counterparts. Further multicenter studies in larger cohorts are needed to further validate these results.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 60%

Expression Patterns of Circulating MicroRNAs in the Risk Stratification of Bicuspid Aortopathy

Girdauskas

Neumann²,

Petersen

et al. 2020

JCM

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“…They found that the expression levels of circulating miR-122, miR-130a, and miR-486 were significantly associated with aortic valve morphology (i.e., bicuspid vs. tricuspid), whereas the downregulation of circulating miR-718 strongly correlated with the proximal aortic diameter and ascending aortic dilation. Our group found a significant downregulation of blood miR-17 and miR-106a in a BAV aortopathy cohort, as well as a strong correlation between aortic root size and blood levels of miR-17 and miR-106a in a pooled cohort of 96 BAV patients [20]. Furthermore, we focused specifically on those patients who underwent an isolated aortic valve surgery due to BAV and had a significant aortopathy progression during the postoperative follow-up (i.e., increase of ascending aortic diameter ≥ 3.0 mm).…”

Section: Circulating Micrornas and Bicuspid Aortopathymentioning

confidence: 52%

Unravelling the Pathogenetic Mechanisms in Congenital Aortopathies: Need for an Integrative Translational Approach

Girdauskas

Kaemmerer

Kodolitsch

2020

JCM

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Congenital heart disease (CHD)-associated aortopathy is a very heterogeneous entity with a wide spectrum of clinical presentations. The pathogenesis of aortopathy is still incompletely understood, and, therefore, the best prevention and management strategy is currently unknown. The most common entity of CHD-associated aortopathies is bicuspid aortic valve (BAV)-associated aortic disease (so called bicuspid aortopathy) that is found in 50%–60% of BAV individuals. BAV aortopathy has been reported in association with an increased risk of aortic events, especially aortic dissection and sudden cardiac death. Risk stratification of adverse aortic events is still very rudimentary and considers only the maximal aortic diameter, which makes it unsuitable for an individual risk prediction. This introductory Editorial highlights the unmet clinical need for more integrative and translational research to unravel pathogenetic pathways in the development of CHD-associated aortopathies, integrating recently identified genetic lesions and knowledge on circulating biomarkers and microstructural changes in the diseased aorta.

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“…The variance may reflect differences in methodology or the known biological heterogeneity that makes BAV-TAA so difficult to study. This is reflected in a more recent study in which the expression of seven miRNAs was analysed according to distinct BAV phenotypic subgroups; those with aortic root dilatation and concomitant insufficiency versus BAV with severe aortic stenosis (Girdauskas et al 2018a). Within the root dilatation subgroup, circulating miR-17 and 106a were significantly increased in the less dilated (< 50 mm) compared to severely dilated (> 50 mm) aortas; however, when compared overall to the aortic stenosis cohort, significant differences were observed in all seven miRNAs (miR-17, miR-16a, miR19a, miR-20a, miR-21, miR-106a and miR-145) (Girdauskas et al 2018b).…”

Section: Circulating Mirnamentioning

confidence: 99%

Epigenetic influences on genetically triggered thoracic aortic aneurysm

et al. 2018

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Genetically triggered thoracic aortic aneurysms (TAAs) account for 30% of all TAAs and can result in early morbidity and mortality in affected individuals. Epigenetic factors are now recognised to influence the phenotype of many genetically triggered conditions and have become an area of interest because of the potential for therapeutic manipulation. Major epigenetic modulators include DNA methylation, histone modification and non-coding RNA. This review examines epigenetic modulators that have been significantly associated with genetically triggered TAAs and their potential utility for translation to clinical practice.

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Evaluation of microribonucleic acids as potential biomarkers in the bicuspid aortic valve-associated aortopathy†

Abstract: Expression of circulating miR-17 and miR-106a in the BAV root phenotype patients correlates with the severity of aortopathy and the risk of adverse aortic events. MicroRNAs have the potential to serve as biomarkers in the BAV-associated aortopathy.

Cited by 17 publications

References 25 publications

Expression Patterns of Circulating MicroRNAs in the Risk Stratification of Bicuspid Aortopathy

Expression Patterns of Circulating MicroRNAs in the Risk Stratification of Bicuspid Aortopathy

Unravelling the Pathogenetic Mechanisms in Congenital Aortopathies: Need for an Integrative Translational Approach

Epigenetic influences on genetically triggered thoracic aortic aneurysm

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