Gene expression in experimental aortic coarctation and repair: candidate genes for therapeutic intervention?
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ABSTRACT:
ORGANISM(S): Oryctolagus cuniculus
PROVIDER: GSE70687 | GEO | 2015/07/10
SECONDARY ACCESSION(S): PRJNA289362
REPOSITORIES: GEO
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Project description:The objective of the current investigation was to use microarray techniques to quantify differentially expressed genes (DEGs) in the upstream aorta subjected to high arterial BP after surgical induction of CoA, and restoration of normal arterial BP after its correction. DEGs may offer additional insight into potential mechanisms of persistent CV morbidity despite successful surgical repair. Male New Zealand white rabbits ~10 weeks old and weighing ~1.0 kg randomly underwent proximal dAo CoA. A 20 mmHg BP gradient was imposed using silk (permanent) or Vicryl (degradable) suture to mimic untreated CoA and surgically corrected CoA, respectively. Rabbits develop a pronounced stenosis and accompanying elevated BP as a stimulus for arterial remodeling within one week. Degradation of Vicryl suture in the corrected group restores aortic diameter close to normal, but with modest residual narrowing. Non-experimental rabbits were designated as a control group. This results in a statistically significant increase in mean, systolic and pulse BP proximal to the coarctation for CoA as compared to both control and corrected rabbits. A ~4 mm circumferential region from the proximal aorta between the coarctation site and left subclavian artery was excised at harvest (32 weeks of age) and frozen. Frozen samples (n=4/group) were shipped overnight to Arraystar, Inc (Rockville, MD) for microarray analysis.
2015-07-10 | E-GEOD-70687 | biostudies-arrayexpress
Project description:Coarctation of the aorta (CoA) is a constriction of the proximal descending thoracic aorta and is one of the most common congenital cardiovascular defects. Treatments for CoA improve life expectancy, but morbidity persists, particularly due to the development of chronic hypertension (HTN). Identifying the mechanisms of morbidity is difficult in humans due to confounding variables such as age at repair, follow-up duration, coarctation severity and concurrent anomalies. We previously developed an experimental model that replicates aortic pathology in humans with CoA without these confounding variables, and mimics correction at various times using dissolvable suture. Here we present the most comprehensive description of differentially expressed genes (DEGs) to date from the pathology of CoA, which were obtained using this model. Aortic samples (n=4/group) from the ascending aorta that experiences elevated blood pressure (BP) from induction of CoA, and restoration of normal BP after its correction, were analyzed by gene expression microarray, and enriched genes were converted to human orthologues. 51 DEGs with >6 fold-change (FC) were used to determine enriched Gene Ontology terms, altered pathways, and association with National Library of Medicine Medical Subject Headers (MeSH) IDs for HTN, cardiovascular disease (CVD) and CoA. The results generated 18 pathways, 4 of which (cell cycle, immune system, hemostasis and metabolism) were shared with MeSH ID's for HTN and CVD, and individual genes were associated with the CoA MeSH ID. A thorough literature search further uncovered association with contractile, cytoskeletal and regulatory proteins related to excitation-contraction coupling and metabolism that may explain the structural and functional changes observed in our experimental model, and ultimately help to unravel the mechanisms responsible for persistent morbidity after treatment for CoA.
| S-EPMC4514739 | biostudies-literature
Project description:Coarctation of the aorta (CoA) is a relatively common congenital heart defect that affects males more often than females. The underlying causes are not known, but a combination of genetic factors and abnormalities linked to embryonic development is suspected. There are only a few studies of the underlying molecular mechanisms in CoA. The aim of the current study was to expand our understanding of the pathogenesis of CoA by characterizing the transcriptome of the coarctation area.
2024-09-19 | GSE263570 | GEO
Project description:The hematopoietic stem cells (HSCs) arise from hemogenic endothelial cells (HECs) in the para-aortic splanchnopleure (P-Sp)/aorta-gonad-mesonephros (AGM) region of mouse embryos. HECs differentiate into HSC precursors and blood progenitors and form intra-aortic hematopoietic clusters (IAHCs) in the aorta. To identify HECs in distinction from endothelial cells, we performed single-cell RNA-seq analysis of cells isolated from the dorsal aorta and its surrounding tissues at E9.5. We found the population of HECs in the arterial endothelial cell cluster. Therefore, our data might elucidate the mechanism of HEC development.
2024-10-16 | GSE271523 | GEO
Project description: Not available
| S-EPMC5757753 | biostudies-literature
Project description:BackgroundIn aortic coarctation, current guidelines recommend reducing pressure gradients that exceed given thresholds. From a physiological standpoint this should ideally improve the energy expenditure of the heart and thus prevent long term organ damage.ObjectivesThe aim was to assess the effects of interventional treatment on external and internal heart power (EHP, IHP) in patients with aortic coarctation and to explore the correlation of these parameters to pressure gradients obtained from heart catheterization.MethodsIn a collective of 52 patients with aortic coarctation 25 patients received stenting and/or balloon angioplasty, and 20 patients underwent MRI before and after an interventional treatment procedure. EHP and IHP were computed based on catheterization and MRI measurements. Along with the power efficiency these were combined in a cardiac energy profile.ResultsBy intervention, the catheter gradient was significantly reduced from 21.8±9.4 to 6.2±6.1mmHg (p<0.001). IHP was significantly reduced after intervention, from 8.03±5.2 to 4.37±2.13W (p < 0.001). EHP was 1.1±0.3 W before and 1.0±0.3W after intervention, p = 0.044. In patients initially presenting with IHP above 5W intervention resulted in a significant reduction in IHP from 10.99±4.74 W to 4.94±2.45W (p<0.001), and a subsequent increase in power efficiency from 14 to 26% (p = 0.005). No significant changes in IHP, EHP or power efficiency were observed in patients initially presenting with IHP < 5W.ConclusionIt was demonstrated that interventional treatment of coarctation resulted in a decrease in IHP. Pressure gradients, as the most widespread clinical parameters in coarctation, did not show any correlation to changes in EHP or IHP. This raises the question of whether they should be the main focus in coarctation interventions. Only patients with high IHP of above 5W showed improvement in IHP and power efficiency after the treatment procedure.Trial registrationclinicaltrials.gov NCT02591940.
| S-EPMC5231370 | biostudies-literature
Project description:ObjectiveSurgery for aortic coarctation repair provides excellent hemodynamic results but may be complicated by musculoskeletal issues. The purpose of the study was to determine the midterm results of a muscle-sparing surgical approach to aortic coarctation repair, with special emphasis on the repair and on the musculoskeletal changes associated with a posterior thoracotomy.MethodsWe included all children with aortic coarctation operated on with our minimally invasive approach between June 2002 and October 2004, with a follow-up of ≥4.5 years. Patients were assessed clinically and echocardiographically. The spine, left chest, and shoulder were assessed clinically and radiographically.ResultsThirty-one children were included. The age at operation ranged from 1 day to 15 months and weight ranged from 980 g to 10 kg. All patients underwent an extended end-to-end anastomosis coarctation repair through a minimal (n = 19) or total-muscle sparing (n = 12) or extrapleural (n = 18) approach. Five patients had an additional enlargement procedure on the aortic arch. 27 patients had no residual or recurrent gradient. Four patients exhibited restenosis, for which 1 underwent a percutaneous angioplasty and 2 underwent surgical reintervention. All patients were free of hypertension. One patient had borderline values. The musculoskeletal assessment was normal in all but 3 patients. Two patients who underwent other subsequent thoracic surgeries developed thoracogenic scoliosis of moderate severity. A third patient had a left winged scapula. No rib fusion or intercostal space enlargement was found.ConclusionsCompared with a conventional approach, our minimally invasive surgical approach led to excellent musculoskeletal outcomes without compromising the hemodynamic results.
| S-EPMC8302918 | biostudies-literature
Project description:Transcriptional profiling of infrarenal aorta from male and female mice (10-weeks old, C57BL/6J), treated with either porcine pancreatic elastase (PPE) local infusion or sham operation (saline infusion). Samples harvested 7 days after treatment. Goal was to examine gene expression in AAA in this model in both genders. Surgical protocol is as described in PMCID: PMC3148686/PMID: 19629030.
2022-03-03 | GSE197748 | GEO
Project description:ObjectivesThis study aimed to explore aortic morphology and the associations between morphological features and cardiovascular function in a population of patients with bicuspid aortic valve, while further assessing differences between patients with repaired coarctation, patients with unrepaired coarctation and patients without coarctation.MethodsThis is a single-centre retrospective study that included patients with available cardiovascular magnetic resonance imaging data and native bicuspid aortic valve diagnosis (n = 525). A statistical shape analysis was performed on patients with a 3-dimensional magnetic imaging resonance (MRI) dataset (n = 108), deriving 3-dimensional aortic reconstructions and computing a mean aortic shape (template) for the whole population as well as for the 3 subgroups of interest (no coarctation, repaired coarctation and unrepaired coarctation). Shape deformations (modes) were computed and correlated with demographic variables, 2-dimensional MRI measurements and volumetric and functional data.ResultsOverall, the results showed that patients with coarctation tended towards a more Gothic arch architecture, with decreased ascending and increased descending aorta diameters, with the unrepaired-aortic coarctation subgroup exhibiting more ascending aorta dilation. Careful assessment of patients with repaired coarctation only revealed that a more Gothic arch, increased descending aorta dimensions and ascending aorta dilation were associated with reduced ejection fraction (P ≤ 0.04), increased end-diastolic volume (P ≤ 0.04) and increased ventricular mass (P ≤ 0.02), with arch morphology distinguishing patients with and without recoarctation (P = 0.05).ConclusionsA statistical shape modelling framework was applied to a bicuspid aortic valve population revealing nuanced differences in arch morphology and demonstrating that morphological features, not immediately described by conventional measurements, can indicate those shape phenotypes associated with compromised function and thus possibly warranting closer follow-up.
| S-EPMC6459283 | biostudies-literature
Project description: Not available
| S-EPMC8307882 | biostudies-literature