TGFBR1 Rare Variant Associated With Thoracic Aortic Aneurysm, Double Chamber Left Ventricle, Coronary Anomaly, and Inducible Ventricular Tachycardia.
Ontology highlight
ABSTRACT:
SUBMITTER: Bravo-Jaimes K
PROVIDER: S-EPMC7285880 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Acute and chronic aortic diseases have been diagnosed and studied by physicians for centuries. Both the diagnosis and treatment of aortic diseases have been steadily improving over time, largely because of increased physician awareness and improvements in diagnostic modalities. This comprehensive review discusses the pathophysiology and risk factors, classification schemes, epidemiology, clinical presentations, diagnostic modalities, management options, and outcomes of various aortic conditions, including acute aortic dissection (and its variants intramural hematoma and penetrating aortic ulcers) and thoracic aortic aneurysms. Literature searches of the PubMed database were conducted using the following keywords: aortic dissection, intramural hematoma, aortic ulcer, and thoracic aortic aneurysm. Retrospective and prospective studies performed within the past 20 years were included in the review; however, most data are from the past 15 years.
| S-EPMC2676130 | biostudies-literature
Project description:Ascending aortic aneurysms are mostly asymptomatic and present a great risk of aortic dissection or perforation. Consequently, ascending aortic aneurysms are a source of lethality with increased age. Biological aging results in progressive attrition of telomeres, which are the repetitive DNA sequences at the end of chromosomes. These telomeres play an important role in protection of genomic DNA from end-to-end fusions. Telomere maintenance and telomere attrition-associated senescence of endothelial and smooth muscle cells have been indicated to be part of the pathogenesis of degenerative vascular diseases. This systematic review provides an overview of telomeres, telomere-associated proteins and telomerase to the formation and progression of aneurysms of the thoracic ascending aorta. A better understanding of telomere regulation in the vascular pathology might provide new therapeutic approaches. Measurements of telomere length and telomerase activity could be potential prognostic biomarkers for increased risk of death in elderly patients suffering from an aortic aneurysm.
| S-EPMC5795955 | biostudies-literature
Project description:Thoracic aortic aneurysms (TAAs) develop secondary to abnormal aortic extracellular matrix remodeling, resulting in a weakened and dilated aortic wall that progressed to rupture if left unattended. Currently, no diagnostic/prognostic tests are available for the detection of TAA disease. This is largely driven by the lack of a large animal model, which would permit longitudinal/mechanistic studies. Accordingly, the objective of the present study was to establish a reproducible porcine model of aortic dilatation, which recapitulates the structural and biochemical changes observed during human TAA development.Descending TAAs were induced in Yorkshire pigs (20-25 kg; n=7) through intra-adventitial injections of collagenase (5 mL, 0.35 mg/mL) and periadventitial application of crystalline CaCl2 (0.5 g). Three weeks after TAA induction, aortas were harvested and tissue was collected for biochemical and histological measurements. A subset of animals underwent MRI preoperatively and at terminal surgery. Results were compared with sham-operated controls (n=6). Three weeks after TAA induction, aortic luminal area increased by 38 ± 13% (P=0.018 versus control). Aortic structural changes included elastic lamellar degradation and decreased collagen content. The protein abundance of matrix metalloproteinases 3, 8, 9, and 12 increased in TAA tissue homogenates, whereas tissue inhibitors of metalloproteinases 1 and 4 decreased.These data demonstrate aortic dilatation, aortic medial degeneration, and alterations in matrix metalloproteinase/tissue inhibitors of metalloproteinase abundance, consistent with TAA formation. This study establishes for the first time a large animal model of TAA that recapitulates the hallmarks of human disease and provides a reproducible test bed for examining diagnostic, prognostic, and therapeutic strategies.
| S-EPMC3840947 | biostudies-literature
Project description:Thoracic aortic aneurysm (TAA) outcomes are worse in women than men, although reasons for sex differences are unknown. Because faster TAA growth is a risk factor for acute aortic syndromes, we sought to determine the role of sex and aneurysm etiology on TAA growth.Eighty-two consecutive unoperated subjects with TAA who had serial aneurysm measurements were recruited. In multivariable linear regression the association of female sex with aneurysm growth rate was assessed after adjustment for potential confounders. We also tested the interaction term sex×aneurysm etiology in the prediction of TAA growth. Seventy-four percent of subjects were men; mean±SD age was 62.4±11.9 years in men and 67.7±10.7 years in women (P=0.06). Forty-seven (57%) subjects had degenerative TAAs, and the remainder had heritable TAAs. Absolute baseline aneurysm size and follow-up time were not different between men and women. Aneurysm growth rate was 1.19±1.15 mm/y in women and 0.59±0.66 mm/y in men (P=0.02). Female sex remained significantly associated with greater aneurysm growth in multivariable analyses (β±SE: 0.35±0.12, P=0.005). In addition, female sex was associated with faster TAA growth only among those with degenerative TAA (β±SE: 0.33±0.08, P=0.0002) and not among those with heritable TAA (P=0.79), with a significant sex×etiology interaction (P=0.001).TAA growth rates are greater in women than men, and this difference is specific to women with degenerative TAAs. Our findings may explain sex differences in TAA outcomes and provide a foundation for future investigations of this topic.
| S-EPMC5523737 | biostudies-other
Project description: Not available
| S-EPMC8441204 | biostudies-literature
Project description: Not available
| S-EPMC4671300 | biostudies-literature
Project description:Left ventricular apical aneurysms are associated with scar-related ventricular tachycardia (VT) in hypertrophic cardiomyopathy patients. We present a patient with apical hypertrophic cardiomyopathy who underwent combined epicardial and endocardial VT ablation of a left ventricular apical aneurysm, necessitating repeat endocardial VT ablation through a recanalized surgical plication.
| S-EPMC11002801 | biostudies-literature
Project description:Thoracic aortic aneurysm is a potentially life-threatening condition in that it places patients at risk for aortic dissection or rupture. However, our modern understanding of the pathogenesis of thoracic aortic aneurysm is quite limited. A genetic predisposition to thoracic aortic aneurysm has been established, and gene discovery in affected families has identified several major categories of gene alterations. The first involves mutations in genes encoding various components of the transforming growth factor beta (TGF-β) signaling cascade (FBN1, TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD2, SMAD3 and SKI), and these conditions are known collectively as the TGF-β vasculopathies. The second set of genes encode components of the smooth muscle contractile apparatus (ACTA2, MYH11, MYLK, and PRKG1), a group called the smooth muscle contraction vasculopathies. Mechanistic hypotheses based on these discoveries have shaped rational therapies, some of which are under clinical evaluation. This review discusses published data on genes involved in thoracic aortic aneurysm and attempts to explain divergent hypotheses of aneurysm origin.
| S-EPMC5031368 | biostudies-literature
Project description:In this study, we identified various cell clusters in human normal/sporadic TAA ascending aorta samples by single-cell RNA sequencing (scRNA-seq), and discovered the senescent vascular smooth muscle cells (VSMCs) significantly increased in TAA samples. Then we explored the molecular basis of TAA progression, and recognized the key regulators and pathways involved in the TAA progression regulation.
2023-12-01 | GSE143921 | GEO
Project description:BackgroundAging enhances most chronic diseases but its impact on human aortic tissue in health and in thoracic aortic aneurysms (TAA) remains unclear.MethodsWe employed a human aortic biorepository of healthy specimens (n=17) and those that underwent surgical repair for TAA (n=20). First, we performed proteomics comparing aortas of healthy donors to aneurysmal specimens, in young (ie, <60 years of age) and old (ie, ≥60 years of age) subjects. Second, we measured proteins, via immunoblotting, involved in mitophagy (ie, Parkin) and also mitochondrial-induced inflammatory pathways, specifically TLR (toll-like receptor) 9, STING (stimulator of interferon genes), and IFN (interferon)-β.ResultsProteomics revealed that aging transformed the aorta both quantitatively and qualitatively from health to TAA. Whereas young aortas exhibited an enrichment of immunologic processes, older aortas exhibited an enrichment of metabolic processes. Immunoblotting revealed that the expression of Parkin directly correlated to subject age in health but inversely to subject age in TAA. In TAA, but not in health, phosphorylation of STING and the expression of IFN-β was impacted by aging regardless of whether subjects had bicuspid or tricuspid valves. In subjects with bicuspid valves and TAAs, TLR9 expression positively correlated with subject age. Interestingly, whereas phosphorylation of STING was inversely correlated with subject age, IFN-β positively correlated with subject age.ConclusionsAging transforms the human aortic proteome from health to TAA, leading to a differential regulation of biological processes. Our results suggest that the development of therapies to mitigate vascular diseases including TAA may need to be modified depending on subject age.
| S-EPMC9339483 | biostudies-literature