Prognostic significance of factor XIIIA promoter methylation status in aneurysmal subarachnoid haemorrhage (aSAH)

Arati, S.; Chetan, G. K.; Sibin, M.K.; Bhat, Dhananjaya I.; Vazhayil, Vikas; Narasingarao, K. V. L.

doi:10.1186/s12872-019-1146-8

Cited by 5 publications

(5 citation statements)

References 44 publications

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“…Statins are known to inhibit the migration and proliferation of white blood cells into the blood vessels, activate cytokines, upregulate the expression and activity of endothelial nitric oxide synthase, improve endothelial reactivity, increase cerebral blood flow, and exert antioxidant effects. It is therefore not surprising that the synergistic effects of multiple mechanisms enhance the prognosis of patients with aSAH (Kotlega et al, 2015 ; Arati et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Optimal Course of Statins for Patients With Aneurysmal Subarachnoid Hemorrhage: Is Longer Treatment Better? A Meta-Analysis of Randomized Controlled Trials

et al. 2021

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Statins are used in clinical practice to prevent from complications such as cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). However, the efficacy and safety of statins are still controversial due to insufficient evidence from randomized controlled trials and inconsistent results of the existing studies. This meta-analysis aimed to systematically review the latest evidence on the time window and complications of statins in aSAH. The randomized controlled trials in the databases of The Cochrane Library, PubMed, Web of Science, Embase, CNKI, and Wanfang from January 2005 to April 2021 were searched and analyzed systematically. Data analysis was performed using Stata version 16.0. The fixed-effects model (M-H method) with effect size risk ratio (RR) was used for subgroups with homogeneity, and the random-effects model (D-L method) with effect size odds ratio (OR) was used for subgroups with heterogeneity. The primary outcomes were poor neurological prognosis and all-cause mortality, and the secondary outcomes were cerebral vasospasm (CVS) and statin-related complications. This study was registered with PROSPERO (International Prospective Register of Systematic Reviews; CRD42021247376). Nine studies comprising 1,464 patients were included. The Jadad score of the patients was 5–7. Meta-analysis showed that poor neurological prognosis was reduced in patients who took oral statins for 14 days (RR, 0.73 [0.55–0.97]; I2 = 0%). Surprisingly, the continuous use of statins for 21 days had no significant effect on neurological prognosis (RR, 1.04 [0.89–1.23]; I2 = 17%). Statins reduced CVS (OR, 0.51 [0.36–0.71]; I2 = 0%) but increased bacteremia (OR, 1.38 [1.01–1.89]; I2 = 0%). In conclusion, a short treatment course of statins over 2 weeks may improve neurological prognosis. Statins were associated with reduced CVS. Based on the pathophysiological characteristics of CVS and the evaluation of prognosis, 2 weeks could be the optimal time window for statin treatment in aSAH, although bacteremia may increase.

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Section: Discussionmentioning

confidence: 99%

Optimal Course of Statins for Patients With Aneurysmal Subarachnoid Hemorrhage: Is Longer Treatment Better? A Meta-Analysis of Randomized Controlled Trials

et al. 2021

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“…Concerning aSAH prognosis, one study explored methylation signatures of Apolipoprotein E ( APOE ) and Factor XIIIA ( F13A ) genes in relation to both aSAH risk and outcome [ 44 ]. F13A is an important enzyme in the blood coagulation system and APOE is involved in regulating inflammatory responses, and both have been associated with aSAH risk [ 45 , 46 ].…”

Section: Resultsmentioning

confidence: 99%

“…Concerning aSAH prognosis, one study explored methylation signatures of Apolipoprotein E (APOE) and Factor XIIIA (F13A) genes in relation to both aSAH risk and outcome [44].…”

Section: Dna-methylationmentioning

confidence: 99%

The Role of Epigenetics in Brain Aneurysm and Subarachnoid Hemorrhage: A Comprehensive Review

Fernández-Pérez,

Macias-Gómez,

Suárez-Pérez

et al. 2024

IJMS

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This comprehensive review explores the emerging field of epigenetics in intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (aSAH). Despite recent advancements, the high mortality of aSAH needs an understanding of its underlying pathophysiology, where epigenetics plays a crucial role. This review synthesizes the current knowledge, focusing on three primary epigenetic mechanisms: DNA methylation, non-coding RNA (ncRNA), and histone modification in IA and aSAH. While DNA methylation studies are relatively limited, they suggest a significant role in the pathogenesis and prognosis of IA and aSAH, highlighting differentially methylated positions in genes presumably involved in these pathologies. However, methodological limitations, including small sample sizes and a lack of diverse population studies, temper these results. The role of ncRNAs, particularly miRNAs, has been more extensively studied, but there are still few studies focused on histone modifications. Despite methodological challenges and inconsistent findings, these studies underscore the involvement of miRNAs in key pathophysiological processes, including vascular smooth muscle regulation and the inflammatory response. This review emphasizes methodological challenges in epigenetic research, advocating for large-scale epigenome-wide association studies integrating genetic and environmental factors, along with longitudinal studies. Such research could unravel the complex mechanisms behind IA and aSAH, guiding the development of targeted therapeutic approaches.

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“…Prominent involvement of immunoglobulins including IGHV6-1 is consistent with recent reports of a potentially pathogenic role for B cells and immunoglobulin deposition in abdominal aortic aneurysm (AAA) [ 37 ], and suggests similar involvement in the descending thoracic aorta. Factor 13A and B are fibrinolytic proteins with gene polymorphisms associated with AAA and hemolytic aneurysmal subarachnoid hemorrhage in the brain [ 38 , 39 ]. One other interesting standouts in the list of informative proteins differentiating aneurysm and dissection was SAA4 (elevated in dissection).…”

Section: Discussionmentioning

confidence: 99%

Differentiation between descending thoracic aortic diseases using machine learning and plasma proteomic signatures

Momenzadeh,

Kreimer,

Guo

et al. 2024

Clin Proteom

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Background Descending thoracic aortic aneurysms and dissections can go undetected until severe and catastrophic, and few clinical indices exist to screen for aneurysms or predict risk of dissection. Methods This study generated a plasma proteomic dataset from 75 patients with descending type B dissection (Type B) and 62 patients with descending thoracic aortic aneurysm (DTAA). Standard statistical approaches were compared to supervised machine learning (ML) algorithms to distinguish Type B from DTAA cases. Quantitatively similar proteins were clustered based on linkage distance from hierarchical clustering and ML models were trained with uncorrelated protein lists across various linkage distances with hyperparameter optimization using fivefold cross validation. Permutation importance (PI) was used for ranking the most important predictor proteins of ML classification between disease states and the proteins among the top 10 PI protein groups were submitted for pathway analysis. Results Of the 1,549 peptides and 198 proteins used in this study, no peptides and only one protein, hemopexin (HPX), were significantly different at an adjusted p < 0.01 between Type B and DTAA cases. The highest performing model on the training set (Support Vector Classifier) and its corresponding linkage distance (0.5) were used for evaluation of the test set, yielding a precision-recall area under the curve of 0.7 to classify between Type B from DTAA cases. The five proteins with the highest PI scores were immunoglobulin heavy variable 6–1 (IGHV6-1), lecithin-cholesterol acyltransferase (LCAT), coagulation factor 12 (F12), HPX, and immunoglobulin heavy variable 4–4 (IGHV4-4). All proteins from the top 10 most important groups generated the following significantly enriched pathways in the plasma of Type B versus DTAA patients: complement activation, humoral immune response, and blood coagulation. Conclusions We conclude that ML may be useful in differentiating the plasma proteome of highly similar disease states that would otherwise not be distinguishable using statistics, and, in such cases, ML may enable prioritizing important proteins for model prediction.

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Prognostic significance of factor XIIIA promoter methylation status in aneurysmal subarachnoid haemorrhage (aSAH)

Cited by 5 publications

References 44 publications

Optimal Course of Statins for Patients With Aneurysmal Subarachnoid Hemorrhage: Is Longer Treatment Better? A Meta-Analysis of Randomized Controlled Trials

Optimal Course of Statins for Patients With Aneurysmal Subarachnoid Hemorrhage: Is Longer Treatment Better? A Meta-Analysis of Randomized Controlled Trials

The Role of Epigenetics in Brain Aneurysm and Subarachnoid Hemorrhage: A Comprehensive Review

Differentiation between descending thoracic aortic diseases using machine learning and plasma proteomic signatures

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