Dataset Information

Adventitial adaptive immune cells are associated with ascending aortic dilatation in patients with a bicuspid aortic valve.

ABSTRACT:

Background

Bicuspid aortic valve (BAV) is associated with ascending aorta aneurysms and dissections. Presently, genetic factors and pathological flow patterns are considered responsible for aneurysm formation in BAV while the exact role of inflammatory processes remains unknown.

Methods

In order to objectify inflammation, we employ a highly sensitive, quantitative immunohistochemistry approach. Whole slides of dissected, dilated and non-dilated ascending aortas from BAV patients were quantitatively analyzed.

Results

Dilated aortas show a 4-fold increase of lymphocytes and a 25-fold increase in B lymphocytes in the adventitia compared to non-dilated aortas. Tertiary lymphoid structures with B cell follicles and helper T cell expansion were identified in dilated and dissected aortas. Dilated aortas were associated with an increase in M1-like macrophages in the aorta media, in contrast the number of M2-like macrophages did not change significantly.

Conclusion

This study finds unexpected large numbers of immune cells in dilating aortas of BAV patients. These findings raise the question whether immune cells in BAV aortopathy are innocent bystanders or contribute to the deterioration of the aortic wall.

SUBMITTER: Staal AHJ

PROVIDER: S-EPMC10086356 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adventitial adaptive immune cells are associated with ascending aortic dilatation in patients with a bicuspid aortic valve.

Staal Alexander H J AHJ Cortenbach Kimberley R G KRG Gorris Mark A J MAJ van der Woude Lieke L LL Srinivas Mangala M Heijmen Robin H RH Geuzebroek Guillaume S C GSC Grewal Nimrat N Hebeda Konnie M KM de Vries I Jolanda M IJM DeRuiter Marco C MC van Kimmenade Roland R J RRJ

Frontiers in cardiovascular medicine 20230328

<h4>Background</h4>Bicuspid aortic valve (BAV) is associated with ascending aorta aneurysms and dissections. Presently, genetic factors and pathological flow patterns are considered responsible for aneurysm formation in BAV while the exact role of inflammatory processes remains unknown.<h4>Methods</h4>In order to objectify inflammation, we employ a highly sensitive, quantitative immunohistochemistry approach. Whole slides of dissected, dilated and non-dilated ascending aortas from BAV patients w ...[more]

PMID: 37057097

Similar Datasets

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.

Project description:BackgroundBicuspid aortic valves (BAV) are frequently associated with ascending aortic aneurysms. The etiology is incompletely understood, but genetic factors, in addition to flow perturbations, are likely involved. Since loss of contractility and elaboration of extracellular matrix in the vessel wall are features of BAV-associated aortopathy, phenotypic modulation of smooth muscle cells (SMCs) may play a role.MethodsAscending aortic tissue was collected intra-operatively from 25 individuals with normal (i.e., tricuspid) aortic valves (TAV) and from 25 individuals with BAVs. For both TAV and BAV, 10 patients had non-dilated (ND) and 15 patients had dilated (D) aortas. SMCs were isolated and cultured from a subset of patients from each group. Aortic tissue and SMCs were fluorescently immunolabeled for SMC phenotypic markers (i.e., alpha-smooth muscle actin (ASMA, contractile), vimentin (synthetic) and p16INK4a and p21Cip1 (senescence). SMCs were also analyzed for replicative senescence in culture.ResultsIn normal-sized and dilated BAV aortas, SMCs switched from the contractile state to either synthetic or senescent phenotypes, as observed by loss of ASMA (ND: P = 0.001, D: P = 0.002) and associated increases in vimentin (ND: P = 0.03, D: P = 0.004) or p16/p21 (ND: P = 0.03, D: P<0.0001) compared to TAV. Dilatation of the aorta exacerbated SMC phenotypic switching in both BAV and TAV aortas (all P<0.05). In SMCs cultured from normal and dilated aortas, those isolated from BAV reached replicative senescence faster than those from TAV aortas (all P = 0.02). Furthermore, there was a stark inverse correlation between ASMA and cell passage number in BAV SMCs (ND: P = 0.0006, D: P = 0.01), but not in TAV SMCs (ND: P = 0.93, D: P = 0.20).ConclusionsThe findings of this study provide direct evidence from cell culture studies implying that SMCs switch from the contractile state to either synthetic or senescent phenotypes in the non-dilated BAV aorta. In cultured SMCs from both non-dilated and dilated aortas, we found that this process may precede dilatation and accompany aneurysm development in BAV. Our findings suggest that therapeutically targeting SMC phenotypic modulation in BAV patients may be a viable option to prevent or delay ascending aortic aneurysm formation.

Project description:BackgroundBicuspid 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.MethodsPlasma 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).ResultsFifteen 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).ConclusionsThis 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.

Dataset Information

Adventitial adaptive immune cells are associated with ascending aortic dilatation in patients with a bicuspid aortic valve.

Background

Methods

Results

Conclusion

Publications

Adventitial adaptive immune cells are associated with ascending aortic dilatation in patients with a bicuspid aortic valve.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets