Genetic Variation in LRP1 Associates with Stanford Type B Aortic Dissection Risk and Clinical Outcome.
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ABSTRACT:
SUBMITTER: Erhart P
PROVIDER: S-EPMC8780592 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Stanford type B aortic dissection is a rare, life-threatening complex phenotype associated with several modifiable and genetic risk factors. In the current study of a hospital-based, consecutive series of aortic dissection patients we propose a selection based on age and family history of aortic disease for genetic testing and detection of causative gene variants.Methods: In this single center cohort study from 2013 to 2018 patients with acute Stanford type B aortic dissections were consecutively treated and analyzed by next generation sequencing based on selection criteria (age of disease onset ?45 years and/or positive familial history for aortic disease) to detect genome-wide pathogenic variants in protein-coding sequences and to identify large copy number variants (CNV). Variants in a predefined panel of 30 genes associated with the familial thoracic aortic aneurysm and dissection (TAAD) syndrome were evaluated.Results: From 105 patients nine matched selection criteria for genetic testing. Next-generation sequencing analysis revealed causal variants in FBN1 (fibrillin-1) in three patients: a pathogenic missense variant [c.6661T>C, p.(Cys2221Arg)] and two truncating variants [c.4786C>T, p.(Arg1596Ter)] and [c.6366C>CA, p.(Asp2123GlufsTer5)]. A fourth patient carried a large (>1,000,000 bp) CNV in the long arm of chromosome 10, deleting eleven genes, including the whole ACTA2 (actin alpha 2) gene. The latter two genetic findings have not been reported before.Conclusions: Selection of patients on the basis of young age and familial inheritance of aortic disease favors the identification of disease-causing genetic variants in a clinical cohort of patients with Stanford type B aortic dissection.
| S-EPMC7711383 | biostudies-literature
Project description:BackgroundGenetic disorders are strongly associated with aortic disease. However, the identities of genetic mutations in sporadic Stanford type A aortic dissection (STAAD) are not clear. The present study analysed the possible genetic mutations of the known pathogenic genes of aortic disease and the clinical characteristics in patients with sporadic STAAD.MethodsWe analysed genetic mutations in 26 genes that underlie aortic aneurysms and dissections in 100 sporadic STAAD patients and 568 healthy controls after whole-genome sequencing (WGS). Clinical features and in-hospital death were determined in all STAAD patients.ResultsIn total, 60 suspicious pathogenic mutations (56 novel and 4 previously reported) in 19 genes were identified in 50% (50/100) of patients, and 14 patients had more than 1 mutation. The ascending aortic diameter was extended in patients with mutations (49.1±12.3 vs. 43.7±11.2 mm, P=0.023), and the DeBakey type I phenotype was more common in patients with mutations in genes that coded extracellular matrix (ECM) components than in patients with mutations in other genes (96.6% vs. 66.7%, P=0.007). Patients with fibrillin-1 (FBN1) mutations were younger than patients without FBN1 mutations (44.7±11.0 vs. 53.5±12.1, P=0.030). Subgroup analyses revealed an increased risk of in-hospital mortality in mutation carriers (44.4% vs. 10.5%, P=0.029) but only in patients who received conservative treatment.ConclusionsHalf of Chinese patients with a sporadic form of STAAD may carry mutations in known pathogenic genes of aortic disease, and these patients may exhibit distinct clinical features and poor clinical outcomes with the use of conservative treatment.
| S-EPMC8339749 | biostudies-literature
Project description:Background: Stanford type A aortic dissection (ATAAD) is a common life-threatening event in the aorta. Recently, immune disorder has been linked to the risk factors that cause ATAAD at the molecular level. However, the specific immune-related gene signature during the progression is unclear. Methods: The GSE52093 and GSE98770 datasets related to ATAAD from the Gene Expression Omnibus (GEO) database were acquired. The immune gene expression levels were analyzed by single sample gene set enrichment analysis (ssGSEA). The correlations between gene networks and immune scores were determined by weighted gene correlation network analysis (WGCNA). The different immune subgroups were finally divided by consensus clustering. The differentially expressed genes (DEGs) were identified and subsequent functional enrichment analyses were conducted. The hub genes were identified by protein-protein interaction (PPI) network and functional similarities analyses. The immune cell infiltration proportion was determined by the CIBERSORT algorithm. Results: According to the ssGSEA results, the 13 ATAAD samples from the GEO database were divided into high- and low-immune subgroups according to the ssGSEA, WGCNA, and consensus clustering analysis results. Sixty-eight immune-related DEGs (IRDEGs) between the two subgroups were enriched in inflammatory-immune response biological processes, including leukocyte cell-cell adhesion, mononuclear cell migration, and myeloid leukocyte migration. Among these IRDEGs, 8 genes (CXCR4, LYN, CCL19, CCL3L3, SELL, F11R, DPP4, and VAV3) were identified as hub genes that represented immune-related signatures in ATAAD after the PPI and functional similarities analyses. The proportions of infiltrating CD8 T cells and M1 macrophages were significantly higher in ATAAD patients in the immune-high group than the immune-low group. Conclusion: Eight immune-related genes were identified as hub genes representing potential biomarkers and therapeutic targets linked to the immune response in ATAAD patients.
| S-EPMC9252449 | biostudies-literature
Project description:BACKGROUND:The purpose of the study was to examine the association between white blood cell count (WBCc) on admission and early outcome in patients with the acute Stanford type A aortic dissection (TAAD). METHODS:From January 2012 to December 2018, we retrospectively evaluated a series of 331 consecutive patients underwent surgery for TAAD in Tongji Hospital. The patients were divided into 2 groups based on the WBCc, i.e. the normal WBCc group (WBCc?11?×?109/L) and leukocytosis group (WBCc>?11?×?109/L). The perioperative data were compared between the 2 groups. The in-hospital mortality and the compositive adverse event including multi-organ dysfunction syndrome, postoperative stroke, tracheotomy, and re-exploration for stopping bleeding were set as end points. Cox regression were used to assess the potential risk factors. RESULTS:The in-hospital mortality was nearly 3 time higher in the leukocytosis group than in the normal WBCc group (20.9% vs.8.1%, P =?0.001), and 15.1% overall. For the circulatory arrest, there was significant higher mortality in patients with leukocytosis than normal WBCc group (26.1%vs.8.9%, P?=?0.001). After adjustment for confounding factors, the leukocytosis was found to be a strong independent predictor of in-hospital mortality (odds ratio?=?3.10; 95% confidence interval 1.38 to 6.97, P?=?0.006). The leukocytosis was also a risk factor of adverse events (odds ratio?=?1.80; 95% confidence interval 1.07 to 3.04, P?=?0.027). CONCLUSIONS:The WBCc within 24?h of admission for TAAD is a strong and independent predictor of in-hospital mortality as well as short-term clinical events. The results of this study have important clinical implications for risk-stratifying patients with TAAD.
| S-EPMC7071739 | biostudies-literature
Project description:Total arch replacement using the frozen elephant trunk procedure is performed for true lumen expansion of the descending aorta in patients with type A acute aortic dissection. However, the remodelling effect of the frozen elephant trunk on the dissected descending aorta is unclear. We aimed to evaluate the effect of the frozen elephant trunk on postoperative descending aortic remodelling after surgery. Between December 2012 and January 2020, we retrospectively investigated 24 patients who underwent total arch replacement using the frozen elephant trunk for type A acute aortic dissection. Remodelling of the descending aorta was evaluated using computed tomography. The aortic remodelling effect, based on aortic true lumen ratio, was determined for (i) DeBakey type (type I versus type III retrograde); (ii) thoracic endovascular aneurysm repair reintervention status (reintervention versus no reintervention); and (iii) stent length of the frozen elephant trunk (60 vs 90 mm). Postoperative true lumen ratio significantly increased in the type I dissection group. The true lumen ratio in the no-reintervention group, which had many patients with the type I dissection, significantly increased after the frozen elephant trunk. Aortic remodelling due to the frozen elephant trunk can be expected after type I acute aortic dissections.
| S-EPMC8691576 | biostudies-literature
Project description:ObjectivesTo compare the efficacy and prognosis of one-stop hybrid surgery using the elephant trunk procedure for treatment of complex Stanford type B aortic dissection.MethodsWe retrospectively analyzed patients who underwent surgical treatment from January 2014 to July 2019. The patients were divided into those who underwent the elephant trunk procedure (n = 10) and those who underwent one-stop hybrid surgery (n = 10). The cardiopulmonary bypass time, mechanical ventilation time, length of hospital stay, and red blood cell usage were compared between the two groups. All patients' 3-month postoperative aortic computed tomography angiography (CTA) findings were also reviewed.ResultsThe cardiopulmonary bypass time, mechanical ventilation time, and length of hospital stay were significantly shorter and red blood cell usage was significantly lower in the one-stop hybridization group. The aortic cross-clamp time was not significantly different between the two groups. Aortic CTA review after hybrid surgery showed that the true lumen of the descending aorta was almost completely restored at 3 months.ConclusionOne-stop hybrid surgery effectively alleviated the occlusion of the aortic dissection, prevented the need for additional surgery, and expanded the indications for covered-stent endovascular repair.
| S-EPMC8020104 | biostudies-literature
Project description:BackgroundAcute Stanford type A aortic dissection is often fatal, with a high mortality rate and requiring emergency intervention. Salvage surgery aims to keep the patient alive by addressing severe aortic regurgitation, tamponade, primary tear, and organ malperfusion and, if possible, prevent the late dissection-related complications in the proximal and downstream aorta. Unfortunately, no optimal standard treatment or technique to treat this disease exists. Total arch replacement with frozen elephant trunk technique plays an important role in treating acute type A aortic dissection. We aim to describe a modified elephant trunk technique and report its short-term outcomes.MethodsFrom February 2018 to August 2019, 16 patients diagnosed with acute Stanford type A aortic dissection underwent surgery with the modified frozen elephant trunk technique at Xiamen Heart Center (male/female: 9/7; average age: 56.1 ± 7.6 years). All perioperative variables were recorded and analyzed. We measured the diameters of the ascending aorta, aortic arch, and descending aorta on the bifurcation of the pulmonary and abdominal aortas and compared the diameters at admission, before discharge, and 3 months after discharge.ResultsFifteen patients (93.8%) had hypertension. The primary tears were located in the lesser curvature of the aortic arch and ascending aorta in 5 (31.3%) and 9 patients (56.3%), respectively, and no entry was found in 2 patients (12.5%). The dissection extended to the iliac artery and distal descending aorta in 14 (87.6%) and 2 patients (12.5%), respectively. The duration of cardiopulmonary bypass (CPB), cross-clamping, and antegrade cerebral perfusion were 215.8 ± 40.5, 140.8 ± 32.3, and 55.1 ± 15.2 min, respectively. Aortic valve repair was performed in 15 patients (93.8%). Bentall procedure was performed in one patient (6.3%). Another patient received coronary artery repair (6.3%). The diameters at all levels were greater on discharge than those on admission, except the aortic arch. After 3 months, the true lumen diameter distal to the frozen elephant trunk increased, indicating false lumen thrombosis and/or aortic remodeling.ConclusionsThe modified frozen elephant trunk technique for acute Stanford type A aortic dissection is safe and feasible and could be used for organ malperfusion. Short-term outcomes are encouraging, but long-term outcomes require further investigation.
| S-EPMC7579979 | biostudies-literature
Project description:Stanford type A aortic dissection (TAAD) is one of the most dangerous diseases of acute aortic syndrome. Molecular pathological studies on TAAD can aid in understanding the disease comprehensively and can provide insights into new diagnostic markers and potential therapeutic targets. In this study, we defined the molecular pathology of TAAD by performing transcriptome sequencing of human ascending aortic tissues. Pathway analysis revealed that activated inflammation, cell death and smooth muscle cell degeneration are the main pathological changes in aortic dissection. However, autophagy is considered to be one of the most important biological processes, regulating inflammatory reactions and degenerative changes. Therefore, we focused on the pathological role of autophagy in aortic dissection and identified 10 autophagy-regulated hub genes, which are all upregulated in TAAD. These results indicate that exaggerated autophagy participates in the pathological process of aortic dissection and may provide new insight for further basic research on TAAD.
| S-EPMC7650806 | biostudies-literature
Project description: Not available
| S-EPMC10122134 | biostudies-literature
Project description:BackgroundAortic dissection is one of the most detrimental cardiovascular diseases with a high risk of mortality and morbidity. This study aimed to examine the key genes and microRNAs associated with Stanford type A aortic dissection (AAD).MethodsThe expression data of AAD and healthy samples were downloaded from two microarray datasets in the Gene Expression Omnibus (GEO) database to identify highly preserved modules by weighted gene co-expression network analysis (WGCNA). Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRNAs) were selected and functionally annotated. The predicted interactions between the DEGs and DEmiRNAs were further illustrated.ResultsIn two highly preserved modules, 459 DEGs were identified. These DEGs were functionally enriched in the HIF1, Notch, and PI3K/Akt pathways. Furthermore, 6 DEmiRNAs that were enriched in the regulation of vasculature development and HIF1 pathway, were predicted to target 23 DEGs.ConclusionsOur study presented several promising modulators, both DEGs and DEmiRNAs, as well as possible pathological pathways for AAD, which narrows the scope for further fundamental research.
| S-EPMC7578500 | biostudies-literature