6 results on '"Baranowska-Clarke AA"'
Search Results
2. Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation.
- Author
-
Adlam D, Berrandou TE, Georges A, Nelson CP, Giannoulatou E, Henry J, Ma L, Blencowe M, Turley TN, Yang ML, Chopade S, Finan C, Braund PS, Sadeg-Sayoud I, Iismaa SE, Kosel ML, Zhou X, Hamby SE, Cheng J, Liu L, Tarr I, Muller DWM, d'Escamard V, King A, Brunham LR, Baranowska-Clarke AA, Debette S, Amouyel P, Olin JW, Patil S, Hesselson SE, Junday K, Kanoni S, Aragam KG, Butterworth AS, Tweet MS, Gulati R, Combaret N, Kadian-Dodov D, Kalman JM, Fatkin D, Hingorani AD, Saw J, Webb TR, Hayes SN, Yang X, Ganesh SK, Olson TM, Kovacic JC, Graham RM, Samani NJ, and Bouatia-Naji N
- Subjects
- Humans, Female, Genome-Wide Association Study, Vascular Diseases genetics, Coronary Artery Disease genetics, Myocardial Infarction
- Abstract
Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
3. Erratum to: Vascular histopathology and connective tissue ultrastructure in spontaneous coronary artery dissection: pathophysiological and clinical implications.
- Author
-
Margaritis M, Saini F, Baranowska-Clarke AA, Parsons S, Vink A, Budgeon C, Allcock N, Wagner BE, Samani NJ, Thüsen JV, Robertus JL, Sheppard MN, and Adlam D
- Published
- 2023
- Full Text
- View/download PDF
4. Exploring the Genetic Architecture of Spontaneous Coronary Artery Dissection Using Whole-Genome Sequencing.
- Author
-
Tarr I, Hesselson S, Iismaa SE, Rath E, Monger S, Troup M, Mishra K, Wong CMY, Hsu PC, Junday K, Humphreys DT, Adlam D, Webb TR, Baranowska-Clarke AA, Hamby SE, Carss KJ, Samani NJ, Bax M, McGrath-Cadell L, Kovacic JC, Dunwoodie SL, Fatkin D, Muller DWM, Graham RM, and Giannoulatou E
- Subjects
- Female, Humans, Acute Coronary Syndrome, Coronary Vessel Anomalies genetics, Vascular Diseases congenital, Vascular Diseases genetics
- Abstract
Background: Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome that predominantly affects women. Its pathophysiology remains unclear but connective tissue disorders (CTD) and other vasculopathies have been observed in many SCAD patients. A genetic component for SCAD is increasingly appreciated, although few genes have been robustly implicated. We sought to clarify the genetic cause of SCAD using targeted and genome-wide methods in a cohort of sporadic cases to identify both common and rare disease-associated variants., Methods: A cohort of 91 unrelated sporadic SCAD cases was investigated for rare, deleterious variants in genes associated with either SCAD or CTD, while new candidate genes were sought using rare variant collapsing analysis and identification of novel loss-of-function variants in genes intolerant to such variation. Finally, 2 SCAD polygenic risk scores were applied to assess the contribution of common variants., Results: We identified 10 cases with at least one rare, likely disease-causing variant in CTD-associated genes, although only one had a CTD phenotype. No genes were significantly associated with SCAD from genome-wide collapsing analysis, however, enrichment for TGF (transforming growth factor)-β signaling pathway genes was found with analysis of 24 genes harboring novel loss-of-function variants. Both polygenic risk scores demonstrated that sporadic SCAD cases have a significantly elevated genetic SCAD risk compared with controls., Conclusions: SCAD shares some genetic overlap with CTD, even in the absence of any major CTD phenotype. Consistent with a complex genetic architecture, SCAD patients also have a higher burden of common variants than controls.
- Published
- 2022
- Full Text
- View/download PDF
5. Vascular histopathology and connective tissue ultrastructure in spontaneous coronary artery dissection: pathophysiological and clinical implications.
- Author
-
Margaritis M, Saini F, Baranowska-Clarke AA, Parsons S, Vink A, Budgeon C, Allcock N, Wagner BE, Samani NJ, von der Thüsen J, Robertus JL, Sheppard MN, and Adlam D
- Subjects
- Connective Tissue, Coronary Angiography methods, Coronary Vessels, Humans, Inflammation, Male, Coronary Vessel Anomalies diagnostic imaging, Coronary Vessel Anomalies etiology, Fibromuscular Dysplasia, Myocardial Infarction pathology, Vascular Diseases congenital
- Abstract
Aims: Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndromes and in rare cases sudden cardiac death (SCD). Connective tissue abnormalities, coronary inflammation, increased coronary vasa vasorum (VV) density, and coronary fibromuscular dysplasia have all been implicated in the pathophysiology of SCAD but have not previously been systematically assessed. We designed a study to investigate the coronary histological and dermal collagen ultrastructural findings in SCAD., Methods and Results: Thirty-six autopsy SCAD cases were compared with 359 SCAD survivors. Coronary and myocardial histology and immunohistochemistry were undertaken. Transmission electron microscopy (TEM) of dermal extracellular matrix (ECM) components of n = 31 SCAD survivors and n = 16 healthy volunteers were compared. Autopsy cases were more likely male (19% vs. 5%; P = 0.0004) with greater proximal left coronary involvement (56% vs. 18%; P < 0.0001) compared to SCAD survivors. N = 24 (66%) of cases showed no myocardial infarction on macro- or microscopic examination consistent with arrhythmogenic death. There was significantly (P < 0.001) higher inflammation in cases with delayed-onset death vs. sudden death and significantly more inflammation surrounding the dissected vs. non-dissected vessel segments. N = 17 (47%) cases showed limited intimal fibro-elastic thickening but no features of fibromuscular dysplasia and no endothelial or internal elastic lamina abnormalities. There were no differences in VV density between SCAD and control cases. TEM revealed no general ultrastructural differences in ECM components or markers of fibroblast metabolic activity., Conclusions: Assessment of SCD requires careful exclusion of SCAD, particularly in cases without myocardial necrosis. Peri-coronary inflammation in SCAD is distinct from vasculitides and likely a reaction to, rather than a cause for SCAD. Coronary fibromuscular dysplasia or increased VV density does not appear pathophysiologically important. Dermal connective tissue changes are not common in SCAD survivors., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)
- Published
- 2022
- Full Text
- View/download PDF
6. Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker.
- Author
-
Lozano-Prieto M, Adlam D, García-Guimaraes M, Sanz-García A, Vera-Tomé P, Rivero F, Cuesta J, Bastante T, Baranowska-Clarke AA, Vara A, Martin-Gayo E, Vicente-Manzanares M, Martín P, Samani NJ, Sánchez-Madrid F, Alfonso F, and de la Fuente H
- Subjects
- Adult, Case-Control Studies, Circulating MicroRNA, Coronary Vessel Anomalies diagnosis, Coronary Vessel Anomalies metabolism, Diagnosis, Differential, Disease Susceptibility, Female, Humans, Male, MicroRNAs blood, Middle Aged, Myocardial Infarction diagnosis, Myocardial Infarction etiology, Myocardial Infarction metabolism, RNA Interference, RNA, Messenger, ROC Curve, Vascular Diseases diagnosis, Vascular Diseases etiology, Vascular Diseases metabolism, Vascular Diseases physiopathology, Biomarkers, Coronary Vessel Anomalies etiology, Coronary Vessel Anomalies physiopathology, Gene Expression Regulation, MicroRNAs genetics, Vascular Diseases congenital
- Abstract
Background: Spontaneous Coronary Artery Dissection (SCAD) is an important cause of acute coronary syndromes, particularly in young to middle-aged women. Differentiating acute SCAD from coronary atherothrombosis remains a major clinical challenge., Methods: A case-control study was used to explore the usefulness of circulating miRNAs to discriminate both clinical entities. The profile of miRNAs was evaluated using an unbiased human RT-PCR platform and confirmed using individual primers. miRNAs were evaluated in plasma samples from acute SCAD and atherothrombotic acute myocardial infarction (AT-AMI) from two independent cohorts; discovery cohort (SCAD n = 15, AT-AMI n = 15), and validation cohort (SCAD n = 11, AT-AMI n = 41) with 9 healthy control subjects. Plasma levels of IL-8, TGFB1, TGBR1, Endothelin-1 and MMP2 were analysed by ELISA assays., Findings: From 15 differentially expressed miRNAs detected in cohort 1, we confirmed in cohort 2 the differential expression of 4 miRNAs: miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p, whose expression was higher in SCAD compared to AT-AMI. The combined expression of these 4 miRNAs showed the best predictive value to distinguish between both entities (AUC: 0.879, 95% CI 0.72-1.0) compared to individual miRNAs. Functional profiling of target genes identified an association with blood vessel biology, TGF-beta pathway and cytoskeletal traction force. ELISA assays showed high plasma levels of IL-8, TGFB1, TGFBR1, Endothelin-1 and MMP2 in SCAD patients compared to AT-AMI., Interpretation: We present a novel signature of plasma miRNAs in patients with SCAD. miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p discriminate SCAD from AT-AMI patients and also shed light on the pathological mechanisms underlying this condition., Funding: Spanish Ministry of Economy and Competitiveness (MINECO): Plan Nacional de Salud SAF2017-82886-R, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV). Fundación BBVA a equipos de Investigación Científica 2018 and from Caixa Banking Foundation under the project code HR17-00016 to F.S.M. Instituto de Salud Carlos III (AES 2019): PI19/00565 to F.R, PI19/00545 to P.M. CAM (S2017/BMD-3671-INFLAMUNE-CM) from Comunidad de Madrid to FSM and PM. The UK SCAD study was supported by BeatSCAD, the British Heart Foundation (BHF) PG/13/96/30608 the NIHR rare disease translational collaboration and the Leicester NIHR Biomedical Research Centre., Competing Interests: Declaration of Competing Interest DA has received in kind support for SCAD genetics research from Astra Zeneca Inc. and research grants for unrelated research from the same Company. He has received funding from Abbott Vascular Inc. to support a clinical research Fellow and has undertaken unrelated consultancy for GE inc. No other authors have potential conflicts of interest to declare., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.