Browsing by Subject "Aortic dissection"

Now showing 1 - 7 of 7
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    Bicuspid Aortic Valve: a Review with Recommendations for Genetic Counseling
    (Springer, 2016-12) Freeze, Samantha L.; Landis, Benjamin J.; Ware, Stephanie M.; Helm, Benjamin M.; Department of Pediatrics, IU School of Medicine
    Bicuspid aortic valve (BAV) is the most common congenital heart defect and falls in the spectrum of left-sided heart defects, also known as left ventricular outflow tract obstructive (LVOTO) defects. BAV is often identified in otherwise healthy, asymptomatic individuals, but it is associated with serious long term health risks including progressive aortic valve disease (stenosis or regurgitation) and thoracic aortic aneurysm and dissection. BAV and other LVOTO defects have high heritability. Although recommendations for cardiac screening of BAV in at-risk relatives exist, there are no standard guidelines for providing genetic counseling to patients and families with BAV. This review describes current knowledge of BAV and associated aortopathy and provides guidance to genetic counselors involved in the care of patients and families with these malformations. The heritability of BAV and recommendations for screening are highlighted. While this review focuses specifically on BAV, the principles are applicable to counseling needs for other LVOTO defects.
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    Cardiac and Vascular Surgeons for the Treatment of Aortic Disease: A Successful Partnership for Decision-Making and Management of Complex Cases
    (Sage, 2021) Capoccia, Massimo; Pal, Soumik; Murphy, Michael; Mireskandari, Maziar; Hoschtitzky, Andreas; Nienaber, Christoph A.; Cheshire, Nicholas J.; Rosendahl, Ulrich P.; Surgery, School of Medicine
    Traditionally, cardiac and vascular surgeons have been treating diseases of the aorta as individual specialists. Neither cardiac nor vascular surgeons have ever considered the aorta as a whole, which can be diseased throughout its length at the same time requiring a more thoughtful and different approach. Aortic dissection and aneurysmal disease may well benefit from a multidisciplinary approach. In the context of this review, we discuss examples of joint operating between cardiac and vascular surgeons that may well become a more routine approach in more units in the future.
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    Chest pain while gardening: a Stanford type A dissection involving the aortic root extending into the iliac arteries-an uncommon and potentially catastrophic disease process
    (BioMed Central, 2019-08-30) Taylor, Gregory M.; Barney, Michael W.; McDowell, Eric L.; Emergency Medicine, School of Medicine
    BACKGROUND: An aortic dissection is an uncommon and potentially catastrophic disease process that carries with it a high morbidity and mortality. The inciting event is a tear in the intimal lining of the aorta. This allows passage of blood through the tear and into the aortic media, resulting in the creation of a false lumen. CASE PRESENTATION: We describe the case of a 71-year-old male with a history of hypertension that suffered a Stanford type A dissection with an intimal flap beginning at the level of the aortic root and extending into the bilateral iliac arteries. His clinical presentation was further complicated by shock, cardiac tamponade, severe coagulopathy, an ischemic right lower extremity, infarction of his thoracic spinal cord, and subacute infarcts secondary to malperfusion and embolic disease. Despite maximal intervention, the patient continued to clinically decline and ultimately died on day 5. CONCLUSION: The clinical presentation of an acute aortic dissection is often atypical and mimics other common disease processes. The signs and symptoms largely depend on the extent of the aortic dissection and the presence or absence of malperfusion. With a mortality increasing by 1-2% for every hour until definitive treatment, early recognition and prompt operative intervention are crucial for patient survival.
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    Crucial Genes in Aortic Dissection Identified by Weighted Gene Coexpression Network Analysis
    (Hindawi, 2022-02-07) Zhang, Hongliang; Chen, Tingting; Zhang, Yunyan; Lin, Jiangbo; Zhao, Wenjun; Shi, Yangyang; Lau, Huichong; Zhang, Yang; Yang, Minjun; Xu, Cheng; Tang, Lijiang; Xu, Baohui; Jiang, Jianjun; Chen, Xiaofeng; Radiation Oncology, School of Medicine
    Background: Aortic dissection (AD) is a lethal vascular disease with high mortality and morbidity. Though AD clinical pathology is well understood, its molecular mechanisms remain unclear. Specifically, gene expression profiling helps illustrate the potential mechanism of aortic dissection in terms of gene regulation and its modification by risk factors. This study was aimed at identifying the genes and molecular mechanisms in aortic dissection through bioinformatics analysis. Method: Nine patients with AD and 10 healthy controls were enrolled. The gene expression in peripheral mononuclear cells was profiled through next-generation RNA sequencing. Analyses including differential expressed gene (DEG) via DEGseq, weighted gene coexpression network (WGCNA), and VisANT were performed to identify crucial genes associated with AD. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was also utilized to analyze Gene Ontology (GO). Results: DEG analysis revealed that 1,113 genes were associated with AD. Of these, 812 genes were markedly reduced, whereas 301 genes were highly expressed, in AD patients. DEGs were rich in certain categories such as MHC class II receptor activity, MHC class II protein complex, and immune response genes. Gene coexpression networks via WGCNA identified 3 gene hub modules, with one positively and 2 negatively correlated with AD, respectively. Specifically, module 37 was the most strongly positively correlated with AD with a correlation coefficient of 0.72. Within module 37, five hub genes (AGFG1, MCEMP1, IRAK3, KCNE1, and CLEC4D) displayed high connectivity and may have clinical significance in the pathogenesis of AD. Conclusion: Our analysis provides the possible association of specific genes and gene modules for the involvement of the immune system in aortic dissection. AGFG1, MCEMP1, IRAK3, KCNE1, and CLEC4D in module M37 were highly connected and strongly linked with AD, suggesting that these genes may help understand the pathogenesis of aortic dissection.
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    Deletion of Socs3 Expression in Aortic Smooth Muscle Cells Ameliorates Aortic Dissection
    (Elsevier, 2020-02) Murphy, Michael P.; King, Justin R.; Leckie, Katherin E.; Surgery, School of Medicine
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    Identification of a common polymorphism in COQ8B acting as a modifier of thoracic aortic aneurysm severity
    (Elsevier, 2022-01-13) Landis, Benjamin J.; Lai, Dongbing; Guo, Dong-Chuan; Corvera, Joel S.; Idrees, Muhammad T.; Stadler, Henry W.; Cuevas, Christian; Needler, Gavin U.; Vujakovich, Courtney E.; Milewicz, Dianna M.; Hinton, Robert B.; Ware, Stephanie M.; Pediatrics, School of Medicine
    Thoracic aortic aneurysm (TAA) predisposes to sudden, life-threatening aortic dissection. The factors that regulate interindividual variability in TAA severity are not well understood. Identifying a molecular basis for this variability has the potential to improve clinical risk stratification and advance mechanistic insight. We previously identified COQ8B, a gene important for biosynthesis of coenzyme Q, as a candidate genetic modifier of TAA severity. Here, we investigated the physiological role of COQ8B in human aortic smooth muscle cells (SMCs) and further tested its genetic association with TAA severity. We find COQ8B protein localizes to mitochondria in SMCs, and loss of mitochondrial COQ8B leads to increased oxidative stress, decreased mitochondrial respiration, and altered expression of SMC contractile genes. Oxidative stress and mitochondrial cristae defects were prevalent in the medial layer of human proximal aortic tissues in patients with TAA, and COQ8B expression was decreased in TAA SMCs compared with controls. A common single nucleotide polymorphism (SNP) rs3865452 in COQ8B (c.521A>G, p.H174R) was associated with decreased rate of aortic root dilation in young patients with TAA. In addition, the SNP was less frequent in a second cohort of early-onset thoracic aortic dissection cases compared with controls. COQ8B protein levels in aortic SMCs were increased in TAA patients homozygous for rs3865452 compared with those homozygous for the reference allele. Thus, COQ8B is important for aortic SMC metabolism, which is dysregulated in TAA, and rs3865452 may decrease TAA severity by increasing COQ8B level. Genotyping rs3865452 may be useful for clinical risk stratification and tailored aortopathy management.
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    Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection
    (Frontiers Media, 2022-08-11) Xu, Cheng; Liu, Xiaowei; Fang, Xiaoxin; Yu, Lei; Lau, Hui Chong; Li, Danlei; Liu, Xiaoman; Li, Haili; Ren, Justin; Xu, Baohui; Jiang, Jianjun; Tang, Lijiang; Chen, Xiaofeng; Radiation Oncology, School of Medicine
    Purpose: This study aims to illustrate the cellular landscape in the aorta of experimental aortic dissection (AD) and elaborate on the smooth muscle cells (SMCs) heterogeneity and functions among various cell types. Methods: Male Apolipoprotein deficient (ApoE-/-) mice at 28 weeks of age were infused with Ang II (2,500 ng/kg/min) to induce AD. Aortas from euthanized mice were harvested after 7 days for 10×Genomics single-cell RNA sequencing (scRNA-seq), followed by the identification of cell types and differentially expressed genes (DEGs). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted. Results: AD was successfully induced in ApoE-/- mice. scRNA-seq identified 15 cell clusters and nine cell types, including non-immune cells (endothelials, fibroblasts, and SMCs) and immune cells (B cells, natural killer T cell, macrophages, dendritic cells, neutrophils, and mast cells). The relative numbers of SMCs were remarkably changed, and seven core DEGs (ACTA2,IL6,CTGF,BGN,ITGA8,THBS1, and CDH5) were identified in SMCs. Moreover, we found SMCs can differentiate into 8 different subtypes through single-cell trajectory analysis. Conclusion: scRNA-seq technology can successfully identify unique cell composition in experimental AD. To our knowledge, this is the first study that provided the complete cellular landscape in AD tissues from mice, seven core DEGs and eight subtypes of SMCs were identified, and the SMCs have evolution from matrix type to inflammatory type.