Bicuspid aortopathy – molecular involvement of microRNAs and MMP-TIMP

Naito, Shokichi; Petersen, Johannes; Sequeira-Gross, Tatiana; Neumann, Niklas; Escobar, Jorge Duque; Zeller, Tanja; Reichenspurner, Hermann; Girdauskas, Evaldas

doi:10.1080/1354750x.2020.1841297

Cited by 7 publications

(7 citation statements)

References 20 publications

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“…In former series, we showed the correlation between aortic miRs and matrix metalloproteinases (MMP)/tissue inhibitors of matrix metalloproteinases (TIMP) [12] and between peripheral whole blood miRs and aortic diameter [10]. Wu et al [13] performed a paired comparison of the miR expression between severely dilated vs. normal appearing, less-dilated aortic samples.…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNAs in the prediction of BAV aortopathy: do the expression patterns correlate between blood and aortic tissue?

Naito¹,

Sequeira-Gross²,

Petersen³

et al. 2022

Rev. Cardiovasc. Med.

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Background:The limitation of aortic size-based criteria is gradually recognized in the prediction of aortic events especially in bicuspid aortic valve (BAV) cohorts, while most aortic events happen in patients with proximal aortic diameters <50 mm. Circulating microRNAs (miRs) have been addressed as a novel tool to improve risk stratification in patients with different aortopathies. We aimed to elucidate the correlation between peripheral whole blood and aortic tissue miRs in order to prove the potential availability as a biomarker in the clinical routine. Methods: All patients who received elective aortic valve repair/replacement ± proximal aortic replacement to BAV disease (n = 65, 2013-2018) were prospectively included. The expression of 10 miRs (miR-1, miR-17, miR-18a, miR-19a, miR-20a, miR-21, miR-106a, miR-133a, miR-143 and miR-145) was analyzed in the intraoperatively acquired aortic tissue as well as in the peripheral blood before the surgery. Results: We found a significant correlation between circulating miRs in the peripheral blood and aortic tissue levels of miR-21 (r = 0.293, p = 0.02), miR-133a (r = 0.43, p = 0.02), miR-143 (r = 0.68, p < 0.001), and miR-145 (r = 0.68, p < 0.001). Further, the multivariate logistic regression analysis revealed an association between blood and aortic tissue miR-143 levels each other (Odds Ratio [OR] 1.29, 95% Confidence Interval [CI] 1.11-1.67, p = 0.02; OR 1.36, 95% CI 1.19-2.01, p = 0.03, respectively) and a blood/aortic miR-143 level to dilated aorta (OR 3.61, 95% CI 1.62-9.02, p = 0.01; OR 2.92, 95% CI 1.81-7.05, p = 0.02, respectively). Conclusions: Our study demonstrates a significant correlation between peripheral whole blood and aortic tissue miRs, confirming the hypothesis that circulating miRs may reflect remodeling processes in the proximal aorta in bicuspid aortopathy patients.

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Section: Discussionmentioning

confidence: 99%

Circulating microRNAs in the prediction of BAV aortopathy: do the expression patterns correlate between blood and aortic tissue?

Naito¹,

Sequeira-Gross²,

Petersen³

et al. 2022

Rev. Cardiovasc. Med.

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“…A high level of MMP-2 and increased levels of miR-17 and miRNAs with the same genetic features as miR-17 were found in a comparative study involving patients with mild and severe aorta dilation, with a decreased level of TIMP -1, TIMP-2, and TIMP-3, thus hypothesizing a continuous development of TA influenced by BAV [ 20 ]. A recent study showed a relationship between miR-133a and TIMP-1 and TIMP-2 without reporting a statistically significant association between miR-143 and MMP-2 [ 21 ].…”

Section: Genetics and Molecular Biologymentioning

confidence: 99%

Patients with Bicuspid Aortopathy and Aortic Dilatation

Nappi

Giacinto

Lusini

et al. 2022

JCM

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(1) Background: Bicuspid aortic valve (BAV) is the most frequent congenital cardiac disease. Alteration of ascending aorta diameter is a consequence of shear stress alterations due to haemodynamic abnormalities developed from inadequate valve cusp coaptation. (2) Objective: This narrative review aims to discuss anatomical, pathophysiological, genetical, ultrasound, and radiological aspects of BAV disease, focusing on BAV classification related to imaging patterns and flux models involved in the onset and developing vessel dilatation. (3) Methods: A comprehensive search strategy was implemented in PubMed from January to May 2022. English language articles were selected independently by two authors and screened according to the following criteria. (4) Key Contents and Findings: Ultrasound scan is the primary step in the diagnostic flowchart identifying structural and doppler patterns of the valve. Computed tomography determines aortic vessel dimensions according to the anatomo-pathology of the valve. Magnetic resonance identifies hemodynamic alterations. New classifications and surgical indications derive from these diagnostic features. Currently, indications correlate morphological results, dissection risk factors, and genetic alterations. Surgical options vary from aortic valve and aortic vessel substitution to aortic valve repair according to the morphology of the valve. In selected patients, transcatheter aortic valve replacement has an even more impact on the treatment choice. (5) Conclusions: Different imaging approaches are an essential part of BAV diagnosis. Morphological classifications influence the surgical outcome.

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“…Another study also suggests that the regulation of specific miRNAs in aortic tissue, specifically miR-133a and miR-143, may affect the development of aneurysms in patients with BAV due to its effects on MMP/TIMP homeostasis [ 70 ].…”

Section: Pieces and Findings Related To Micrornas And Other Regulatory Rnasmentioning

confidence: 99%

Update in Biomolecular and Genetic Bases of Bicuspid Aortopathy

Junco-Vicente

Río-García

Martı́n

et al. 2021

IJMS

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Bicuspid aortic valve (BAV) associated with aortopathy is the most common congenital heart disease in the general population. Far from being a simple harmless valve malformation, it can be a complex and heterogeneous disease and a source of chronic and acute pathology (early valvular disease, aneurysm, dissection). In the previous years, intense research has been carried out to find out and understand its mechanisms, but the pathophysiology of the disease is still not fully understood and many questions remain open. Recent studies have discovered several genetic mutations involved in the development of valvular and aortic malformations, but still cannot explain more than 5–10% of cases. Other studies have also focused on molecular alterations and cellular processes (TGF-β pathway, microRNAs, degradation of the extracellular matrix, metalloproteinases, etc.), being a field in constant search and development, looking for a therapeutic target to prevent the development of the disease. Increased knowledge about this multifaceted disorder, derived from both basic and clinical research, may influence the diagnosis, follow-up, prognosis, and therapies of affected patients in the near future. This review focuses on the latest and outstanding developments on the molecular and genetic investigations of the bicuspid aortopathy.

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Bicuspid aortopathy – molecular involvement of microRNAs and MMP-TIMP

Cited by 7 publications

References 20 publications

Circulating microRNAs in the prediction of BAV aortopathy: do the expression patterns correlate between blood and aortic tissue?

Circulating microRNAs in the prediction of BAV aortopathy: do the expression patterns correlate between blood and aortic tissue?

Patients with Bicuspid Aortopathy and Aortic Dilatation

Update in Biomolecular and Genetic Bases of Bicuspid Aortopathy

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