Dataset Information

Medial tunica degeneration of the ascending aortic wall is associated with specific microRNA changes in bicuspid aortic valve disease.

ABSTRACT: Ascending aortic diameter is not an accurate parameter for surgical indication in patients with bicuspid aortic valve (BAV). Thus, the present study aimed to identify specific microRNAs (miRNAs/miRs) and their expression levels in aortic wall aneurysm associated with BAV according to severity of medial degeneration and to elucidate the association between the tissue expression levels of the miRNAs with their expression in plasma. Aortic wall and blood specimens were obtained from 38 patients: 12 controls and 26 patients with BAV with ascending aortic aneurysm. Of the patients with BAV, 19 had cusp fusions of right and left, 5 of right and non‑coronary, and 2 of left and non‑coronary. Two groups of patients were identified according to the grade of medial degeneration (MD): Low‑grade D group (LGMD) and high‑grade MD group (HGMD). Expression level of miR‑122, miR‑130, miR‑718 and miR‑486 were validated by reverse transcription‑quantitative PCR in plasma and tissue samples. MD grade was found to be independent from the BAV phenotype. The HGD group showed increased expression levels of MMP‑9 and MMP‑2, and an increase in the number of apoptotic cells. Tissue expression levels of miR‑718 and miR‑122 were lower in the LGMD and HGD groups compared with expression in the control group; the HGD group showed increased levels of miR‑486. Plasma expression levels of miR‑122 were decreased in the LGMD and HGD groups, and miR‑718 was only reduced in the HGD group. On the contrary, expression of miR‑486 was increased in the LGMD and HGD groups. The data suggested that miR‑486 may be considered as a non‑invasive biomarker of aortic wall degeneration. Dysregulation of this putative biomarker may be associated with high risk of dissection and rupture in patients with BAV.

SUBMITTER: Pisano C

PROVIDER: S-EPMC8569523 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveGuidelines for repair of bicuspid aortic valve-associated ascending thoracic aortic aneurysms have been changing, most recently to the same criteria as tricuspid aortic valve-ascending thoracic aortic aneurysms. Rupture/dissection occurs when wall stress exceeds wall strength. Recent studies suggest similar strength of bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms; thus, comparative wall stress may better predict dissection in bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms. Our aim was to determine whether bicuspid aortic valve-ascending thoracic aortic aneurysms had higher wall stresses than their tricuspid aortic valve counterparts.MethodsPatients with bicuspid aortic valve- and tricuspid aortic valve-ascending thoracic aortic aneurysms (bicuspid aortic valve = 17, tricuspid aortic valve = 19) greater than 4.5 cm underwent electrocardiogram-gated computed tomography angiography. Patient-specific 3-dimensional geometry was reconstructed and loaded to systemic pressure after accounting for prestress geometry. Finite element analyses were performed using the LS-DYNA solver (LSTC Inc, Livermore, Calif) with user-defined fiber-embedded material model to determine ascending thoracic aortic aneurysm wall stress.ResultsBicuspid aortic valve-ascending thoracic aortic aneurysms 99th-percentile longitudinal stresses were 280 kPa versus 242 kPa (P = .028) for tricuspid aortic valve-ascending thoracic aortic aneurysms in systole. These stresses did not correlate to diameter for bicuspid aortic valve-ascending thoracic aortic aneurysms (r = -0.004) but had better correlation to tricuspid aortic valve-ascending thoracic aortic aneurysms diameter (r = 0.677). Longitudinal stresses on sinotubular junction were significantly higher in bicuspid aortic valve-ascending thoracic aortic aneurysms than in tricuspid aortic valve-ascending thoracic aortic aneurysms (405 vs 329 kPa, P = .023). Bicuspid aortic valve-ascending thoracic aortic aneurysm 99th-percentile circumferential stresses were 548 kPa versus 462 kPa (P = .033) for tricuspid aortic valve-ascending thoracic aortic aneurysms, which also did not correlate to bicuspid aortic valve-ascending thoracic aortic aneurysm diameter (r = 0.007).ConclusionsCircumferential and longitudinal stresses were greater in bicuspid aortic valve- than tricuspid aortic valve-ascending thoracic aortic aneurysms and were more pronounced in the sinotubular junction. Peak wall stress did not correlate with bicuspid aortic valve-ascending thoracic aortic aneurysm diameter, suggesting diameter alone in this population may be a poor predictor of dissection risk. Our results highlight the need for patient-specific aneurysm wall stress analysis for accurate dissection risk prediction.

Project description:BACKGROUND:Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality affecting 1-2% of the population and is associated with a significantly increased risk of ascending aortic aneurysm. However, predicting which patients will develop aneurysms remains a challenge. This pilot study aimed to identify candidate plasma biomarkers for monitoring ascending aortic diameter and predicting risk of future aneurysm in BAV patients. METHODS:Plasma samples were collected pre-operatively from BAV patients undergoing aortic valve surgery. Maximum ascending aortic diameter was measured on pre-operative transoesophageal echocardiography. Maximum diameter???45 mm was classified as aneurysmal. Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH-MS), an advanced mass spectrometry technique, was used to identify and quantify all proteins within the samples. Protein abundance and aortic diameter were correlated using logistic regression. Levene's test was used to identify proteins demonstrating low abundance variability in the aneurysmal patients (consistent expression in disease), and high variability in the non-aneurysmal patients (differential expression between 'at risk' and not 'at risk' patients). RESULTS:Fifteen plasma samples were collected (seven non-aneurysmal and 8 aneurysmal BAV patients). The mean age of the patients was 55.5 years and the majority were female (10/15, 67%). Four proteins (haemoglobin subunits alpha, beta and delta and mannan-binding lectin serine protease) correlated significantly with maximal ascending aortic diameter (p?<?0.05, r?=?0.5-0.6). Five plasma proteins demonstrated significantly lower variability in the aneurysmal group and may indicate increased risk of aneurysm in non-aneurysmal patients (DNA-dependent protein kinase catalytic subunit, lumican, tetranectin, gelsolin and cartilage acidic protein 1). A further 7 proteins were identified only in the aneurysmal group (matrin-3, glucose-6-phosphate isomerase, coactosin-like protein, peptidyl-prolyl cis-trans isomerase A, golgin subfamily B member 1, myeloperoxidase and 2'-deoxynucleoside 5'-phosphate N-hydrolase 1). CONCLUSIONS:This study is the first to identify candidate plasma biomarkers for predicting aortic diameter and risk of future aneurysm in BAV patients. It provides valuable pilot data and proof of principle that could be used to design a large-scale prospective investigation. Ultimately, a more affordable 'off-the-shelf' follow-on blood assay could then be developed in place of SWATH-MS, for use in the healthcare setting.

Project description:ObjectiveAscending thoracic aortic aneurysm (ATAA) in patients with bicuspid aortic valve (BAV) commonly dilate asymmetrically compared with patients with tricuspid aortic valve (TAV). This discrepancy in aneurysm geometry led us to hypothesize that microarchitectural differences underlie the observed asymmetric dilatation pattern. The purpose of this study was to characterize the microarchitectural distinctions of the extracellular matrix of the 2 phenotypes with a focus on the proportion of radially oriented elastin and collagen fibers in different circumferential aortic regions.MethodsAortic tissue rings were obtained just distal to the sinotubular junction from patients with BAV or TAV undergoing elective aneurysm repair. They were sectioned into three circumferentially based regions according to adjacent aortic sinus segment (left coronary sinus [L], right coronary sinus [R], or noncoronary sinus [N]). Multiphoton microscopy was used to quantify and characterize the number of radially oriented elastin and collagen fibers.ResultsThere were fewer radially oriented fibers in medial region N and medial-intimal region R of BAV-ATAAs when compared with TAV-ATAAs (medial region N, amplitude of angular undulation of elastin = 10.67° ± 1.35° vs 15.58° ± 1.91°; P = .041; medial-intimal region R, amplitude of angular undulation of elastin = 9.83° ± 0.83° vs 14.72° ± 1.64°; P = .015). Conversely, fibers became more radially oriented in the medial-intimal region L of BAV-ATAA when compared with TAV-ATAA (amplitude of angular undulation of collagen = 18.67° ± 0.95° vs 14.56° ± 1.37°; P = .041).ConclusionsThe differential pattern of fiber orientation noted between L and N-R regions help explain the unique pattern of greater curvature dilatation of BAV-ATAA. The distinctions noted in matrix microarchitecture may form the basis of differing aneurysm geometries and aortic wall integrities in ATAAs arising in these different valve morphologies.

Dataset Information

Medial tunica degeneration of the ascending aortic wall is associated with specific microRNA changes in bicuspid aortic valve disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets