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Visualization and Analysis of Gene Expression in Stanford Type A Aortic Dissection Tissue Section by Spatial Transcriptomics.

ABSTRACT: Background: Spatial transcriptomics enables gene expression events to be pinpointed to a specific location in biological tissues. We developed a molecular approach for low-cell and high-fiber Stanford type A aortic dissection and preliminarily explored and visualized the heterogeneity of ascending aortic types and mapping cell-type-specific gene expression to specific anatomical domains. Methods: We collected aortic samples from 15 patients with Stanford type A aortic dissection and a case of ascending aorta was randomly selected followed by 10x Genomics and spatial transcriptomics sequencing. In data processing of normalization, component analysis and dimensionality reduction analysis, different algorithms were compared to establish the pipeline suitable for human aortic tissue. Results: We identified 19,879 genes based on the count level of gene expression at different locations and they were divided into seven groups based on gene expression trends. Major cell that the population may contain are indicated, and we can find different main distribution of different cell types, among which the tearing sites were mainly macrophages and stem cells. The gene expression of these different locations and the cell types they may contain are correlated and discussed in terms of their involvement in immunity, regulation of oxygen homeostasis, regulation of cell structure and basic function. Conclusion: This approach provides a spatially resolved transcriptome- and tissue-wide perspective of the adult human aorta and will allow the application of human fibrous aortic tissues without any effect on genes in different layers with low RNA expression levels. Our findings will pave the way toward both a better understanding of Stanford type A aortic dissection pathogenesis and heterogeneity and the implementation of more effective personalized therapeutic approaches.

SUBMITTER: Li YH

PROVIDER: S-EPMC8275070 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

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.

Project description:BackgroundThis research aimed to evaluate the impacts of transfusing packed red blood cells (pRBCs), fresh frozen plasma (FFP), or platelet concentrate (PC) on postoperative mechanical ventilation time (MVT) in patients with acute Stanford type A aortic dissection (ATAAD) undergoing after total arch replacement (TAR).MethodsThe clinical data of 384 patients with ATAAD after TAR were retrospectively collected from December 2015 to October 2017 to verify whether pRBCs, FFP, or PC transfusion volumes were associated with postoperative MVT. The logistic regression was used to assess whether blood products were risk factors for prolonged mechanical ventilation (PMV) in all three endpoints (PMV ≥24 h, ≥48 h, and ≥72 h).ResultsThe mean age of 384 patients was 47.6 ± 10.689 years, and 301 (78.39%) patients were men. Median MVT was 29.5 (4-574) h (h), and 213 (55.47%), 136 (35.42%), and 96 (25.00%) patients had PMV ≥24 h, ≥48 h, and ≥72 h, respectively. A total of 36 (9.38%) patients did not have any blood product transfusion, the number of patients with transfusion of pRBCs, FFP, and PC were 334 (86.98%), 286 (74.48%), and 189 (49.22%), respectively. According to the multivariate logistic regression of three PMV time-endpoints, age was a risk factor [PMV ≥ 24 h odds ratio (OR PMV≥24) = 1.045, p = 0.005; OR PMV≥48 = 1.060, p = 0.002; OR PMV≥72 = 1.051, p = 0.011]. pRBC transfusion (OR PMV≥24 = 1.156, p = 0.001; OR PMV≥48 = 1.156, p < 0.001; OR PMV≥72 = 1.135, p ≤ 0.001) and PC transfusion (OR PMV≥24 = 1.366, p = 0.029; OR PMV≥48 = 1.226, p = 0.030; OR PMV≥72 = 1.229, p = 0.011) were independent risk factors for PMV. FFP had no noticeable effect on PMV [OR PMV≥48 = 0.999, 95% confidence interval (CI) 0.998-1.000, p = 0.039; OR PMV≥72 = 0.999, 95% CI: 0.998-1.000, p = 0.025].ConclusionsIn patients with ATAAD after TAR, the incidence of PMV was very high. Blood products transfusion was closely related to postoperative mechanical ventilation time. pRBC and PC transfusions and age increased the incidence of PMV at all three endpoints.

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Visualization and Analysis of Gene Expression in Stanford Type A Aortic Dissection Tissue Section by Spatial Transcriptomics.

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