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

Naito, Shokichi; Sequeira-Gross, Tatiana; Petersen, Johannes; Detlef, Inken; Sachse, Marco; Zeller, Tanja; Reichenspurner, Hermann; Girdauskas, Evaldas

doi:10.31083/j.rcm2302047

Cited by 3 publications

(3 citation statements)

References 32 publications

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“…One compelling topic in recent primary literature includes detailed characterization and mechanistic exploration of aorta-specific microRNAs that are differentially expressed in patients with BAV aortopathy [38 ▪ ,39 ▪ ]. These data suggest circulating microRNAs may serve as plasma biomarkers for bicuspid aortopathy, which could help risk-stratify disease and guide the development of precision medicine and pharmaceutical targets to attenuate or prevent dilation.…”

Section: Pathologic Mechanisms As Future Prognostic Markersmentioning

confidence: 99%

Bicuspid aortic valve and its ascending aortopathy

Dunne

Lacro

Flyer

2023

Current Opinion in Pediatrics

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Purpose of review To synthesize and critically assess recent clinical and research advancements in pediatric bicuspid aortic valve (BAV) and its associated aortopathy. Recent findings In pediatric patients with BAV, progressive aortic dilation (i.e. bicuspid aortopathy) is commonly present and associated with increased risk for aortic aneurysm, dissection, and surgery in adulthood. Ongoing research explores the cause, incidence, and progression of bicuspid aortopathy to promote earlier diagnosis and improve preventive management. Recent findings include: high familial incidence and need for improved familial screening; safety of recreational physical activity in most affected children; potential for medical management to slow aortic growth; feasibility of pediatric registries to evaluate longitudinal outcomes; and potential genetic and hemodynamic biomarkers for disease risk stratification. Summary Pediatric bicuspid aortopathy is an important area for investigation and preventive management to improve long-term cardiovascular outcomes. Recent literature promotes familial screening, recreational exercise, medical prophylaxis, registry-based longitudinal evaluation, and continued scientific inquiry.

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Section: Pathologic Mechanisms As Future Prognostic Markersmentioning

confidence: 99%

Bicuspid aortic valve and its ascending aortopathy

Dunne

Lacro

Flyer

2023

Current Opinion in Pediatrics

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“…Upregulated in periodontal ligament stem cells [61]. Associated with aortopathy patients [62]. Over-expression reduced fibrosis, hypertrophy, and apoptosis of cardiomyocytes in heart failure [63].…”

Section: Mir-18a Mimat0000528mentioning

confidence: 99%

Unique miRomics Expression Profiles in Tannerella forsythia-Infected Mandibles during Periodontitis Using Machine Learning

Aravindraja,

Jeepipalli,

Duncan

et al. 2023

IJMS

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T. forsythia is a subgingival periodontal bacterium constituting the subgingival pathogenic polymicrobial milieu during periodontitis (PD). miRNAs play a pivotal role in maintaining periodontal tissue homeostasis at the transcriptional, post-transcriptional, and epigenetic levels. The aim of this study was to characterize the global microRNAs (miRNA, miR) expression kinetics in 8- and 16-week-old T. forsythia-infected C57BL/6J mouse mandibles and to identify the miRNA bacterial biomarkers of disease process at specific time points. We examined the differential expression (DE) of miRNAs in mouse mandibles (n = 10) using high-throughput NanoString nCounter® miRNA expression panels, which provided significant advantages over specific candidate miRNA or pathway analyses. All the T. forsythia-infected mice at two specific time points showed bacterial colonization (100%) in the gingival surface, along with a significant increase in alveolar bone resorption (ABR) (p < 0.0001). We performed a NanoString analysis of specific miRNA signatures, miRNA target pathways, and gene network analysis. A total of 115 miRNAs were DE in the mandible tissue during 8 and 16 weeks The T. forsythia infection, compared with sham infection, and the majority (99) of DE miRNAs were downregulated. nCounter miRNA expression kinetics identified 67 downregulated miRNAs (e.g., miR-375, miR-200c, miR-200b, miR-34b-5p, miR-141) during an 8-week infection, whereas 16 upregulated miRNAs (e.g., miR-1902, miR-let-7c, miR-146a) and 32 downregulated miRNAs (e.g., miR-2135, miR-720, miR-376c) were identified during a 16-week infection. Two miRNAs, miR-375 and miR-200c, were highly downregulated with >twofold change during an 8-week infection. Six miRNAs in the 8-week infection (miR-200b, miR-141, miR-205, miR-423-3p, miR-141-3p, miR-34a-5p) and two miRNAs in the 16-week infection (miR-27a-3p, miR-15a-5p) that were downregulated have also been reported in the gingival tissue and saliva of periodontitis patients. This preclinical in vivo study identified T. forsythia-specific miRNAs (miR-let-7c, miR-210, miR-146a, miR-423-5p, miR-24, miR-218, miR-26b, miR-23a-3p) and these miRs have also been reported in the gingival tissues and saliva of periodontitis patients. Further, several DE miRNAs that are significantly upregulated (e.g., miR-101b, miR-218, miR-127, miR-24) are also associated with many systemic diseases such as atherosclerosis, Alzheimer’s disease, rheumatoid arthritis, osteoarthritis, diabetes, obesity, and several cancers. In addition to DE analysis, we utilized the XGBoost (eXtreme Gradient boost) and Random Forest machine learning (ML) algorithms to assess the impact that the number of miRNA copies has on predicting whether a mouse is infected. XGBoost found that miR-339-5p was most predictive for mice infection at 16 weeks. miR-592-5p was most predictive for mice infection at 8 weeks and also when the 8-week and 16-week results were grouped together. Random Forest predicted miR-592 as most predictive at 8 weeks as well as the combined 8-week and 16-week results, but miR-423-5p was most predictive at 16 weeks. In conclusion, the expression levels of miR-375 and miR-200c family differed significantly during disease process, and these miRNAs establishes a link between T. forsythia and development of periodontitis genesis, offering new insights regarding the pathobiology of this bacterium.

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“…Plasma exosomal miR-423-5p regulates TGF-β signaling by targeting “similar mothers against decapentaplegic Drosophila gene” 2 (SMAD2), exerting functions in the initiation and development of BAV disease and its complication, bicuspid aortopathy [ 22 , 23 ]. Circulating miRNAs may reflect remodeling processes in the proximal aorta in patients with bicuspid aortopathy, and a recent study found a significant association between miRNA expression in peripheral blood and aortic tissue, as levels of miR-21, miR-133a, miR-143, and miR-145 were associated with dilated aorta [ 24 ].…”

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

Cited by 3 publications

References 32 publications

Bicuspid aortic valve and its ascending aortopathy

Bicuspid aortic valve and its ascending aortopathy

Unique miRomics Expression Profiles in Tannerella forsythia-Infected Mandibles during Periodontitis Using Machine Learning

Patients with Bicuspid Aortopathy and Aortic Dilatation

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