Proteomics of Atrial Fibrillation

Souza, Ayesha I. De; Camm, A. John

doi:10.1161/circep.112.973008

Cited by 6 publications

(4 citation statements)

References 47 publications

(50 reference statements)

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“…Previous studies investigating mechanisms of AF using the goat model have shown structural, electrical, contractile and molecular changes during AF (some examples include Ausma et al (2003), Wijffels et al (1995) Allessie et al (2002), van Hunnik et al (2018 and Neuberger et al (2006)) Proteomics studies have been performed in many cardiac diseases including AF (Liu et al, 2020) and reviewed by (De Souza & Camm, 2012) and have highlighted the need for more multi-omics research to investigate possible implicated molecular pathways in the development of AF. In this study we have focussed on changes in endolysosome-related proteins as another factor with a slower time course of development, and their involvement in this disease.…”

Section: Discussionmentioning

confidence: 99%

“…(2018) and Neuberger et al . (2006)) Proteomics studies have been performed in many cardiac diseases including AF (Liu et al ., 2020) and reviewed by (De Souza & Camm, 2012) and have highlighted the need for more multi-omics research to investigate possible implicated molecular pathways in the development of AF. In this study we have focussed on changes in endolysosome-related proteins as another factor with a slower time course of development, and their involvement in this disease.…”

Section: Discussionmentioning

confidence: 99%

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Compartmentalisation proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation

Ayagama

Charles

Bose

et al. 2023

Preprint

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Endolysosomes (EL) are known for their role in regulating both intracellular trafficking and proteostasis. EL help facilitate elimination of damaged membrane and cytosolic proteins, protein aggregates, membranous organelles and also play an important role in calcium signalling. Despite the importance of EL, their specific role in cardiovascular disease is not well understood. In particular, it's unclear how EL contribute to atrial pathology over longer time frames. To shed light on this question, we conducted a comprehensive analysis that involved proteomics, transcriptomics, integrated analysis, electron tomography, western blotting, and enzyme assays. To identify the role of EL in atrial fibrillation (AF), we applied a recently published organelle protein isolation method. We used this method to study biopsies from AF goat model and analyse the EL-specific proteins and pathways involved in this condition. Our results revealed the upregulation of the AMPK pathway and the expression of EL-specific proteins that were not found in whole tissue lysates (TL), including GAA, DYNLRB1, CLTB, SIRT3, CCT2, and muscle-specific HSPB2. We also observed structural anomalies, such as autophago-vacuole formation, irregularly shaped mitochondria, and glycogen deposition, which provide insights into the EL's contribution to AF and related pathways and molecular mechanisms. Overall, our findings suggest that EL play an important role in the development of AF over longer time frames, and provide a more detailed understanding of the underlying molecular processes involved.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Compartmentalisation proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation

Ayagama

Charles

Bose

et al. 2023

Preprint

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“…Finally, in conjunction with the advancement of recent approaches, profiling studies may facilitate integration of clinical information with multiomics data 61 . Combining these data with genomic 62 , 63 , transcriptomic 64 , proteomic 65 , 66 , and metabolomics 67 datasets may provide deeper insights into the underlying mechanisms of AF, from initiation to recurrence to progression, and expedite the design of targeted intervention and therapeutic strategies. Future studies may aim to characterize the eicosanoid metabolites and identify their precise involvement in signaling pathways, i.e., their production, degradation, and activities that may lead to pro-, anti-, or resolving-inflammatory processes more deeply.…”

Section: Discussionmentioning

confidence: 99%

The association between eicosanoids and incident atrial fibrillation in the Framingham Heart Study

Kornej

Qadan

Alotaibi

et al. 2022

Sci Rep

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Chronic inflammation is a continuous low-grade activation of the systemic immune response. Whereas downstream inflammatory markers are associated with atrial fibrillation (AF), upstream inflammatory effectors including eicosanoids are less studied. To examine the association between eicosanoids and incident AF. We used a liquid chromatography-mass spectrometry for the non-targeted measurement of 161 eicosanoids and eicosanoid-related metabolites in the Framingham Heart Study. The association of each eicosanoid and incident AF was assessed using Cox proportional hazards models and adjusted for AF risk factors, including age, sex, height, weight, systolic/diastolic blood pressure, current smoking, antihypertensive medication, diabetes, history of myocardial infarction and heart failure. False discovery rate (FDR) was used to adjust for multiple testing. Eicosanoids with FDR < 0.05 were considered significant. In total, 2676 AF-free individuals (mean age 66 ± 9 years, 56% females) were followed for mean 10.8 ± 3.4 years; 351 participants developed incident AF. Six eicosanoids were associated with incident AF after adjusting for multiple testing (FDR < 0.05). A joint score was built from the top eicosanoids weighted by their effect sizes, which was associated with incident AF (HR = 2.72, CI = 1.71–4.31, P = 2.1 × 10–5). In conclusion, six eicosanoids were associated with incident AF after adjusting for clinical risk factors for AF.

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“…Several small molecules and proteins such as heat-shock proteins (e.g. crystallin ab), antioxidative proteins (peroxiredoxin 1), cytoskeletal proteins (desmin, tubulin), contractile proteins (myosin light chain 1) and metabolic enzymes consistently linked to AF have been identified; however, whether these have any causal relation to AF or are merely associated with underlying structural heart disease remains unknown [110]. In the ARIC (Atherosclerosis Risk in Communities), eight metabolites were significantly associated with AF risk, and two of these, the bile acids glycolithocholate and glycocholenate, remained significantly associated after adjusting for clinical risk factors [111].…”

Section: Proteomics and Metabolomicsmentioning

confidence: 99%

The changing circumstance of atrial fibrillation ‐ progress towards precision medicine

et al. 2016

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The prevalence of atrial fibrillation (AF) in the general population is between 1% and 2% in the developed world and is higher in men than in women. The arrhythmia occurs much more commonly in the elderly, and the estimated lifetime risk of developing AF is one in four for men and women aged 40 years and above. Projected data from multiple population-based studies in the USA and Europe predict a two-to threefold increase in the number of AF patients by 2060. The high lifetime risk of AF and increased longevity underscore the important public health burden posed by this arrhythmia worldwide. AF has multiple aetiologies and a broad variety of presentations. The primary pathologies underlying or promoting the occurrence of AF vary more than for any other cardiac arrhythmia, ranging from autonomic imbalance to organic heart disease and metabolic disorders, such as diabetes mellitus, metabolic syndrome, hyperthyroidism and kidney disease, and lifestyle factors such as smoking, alcohol consumption and participation in endurance sports. Biomarkers are increasingly being investigated and, together with clinical and genetic factors, will eventually lead to a clinically valuable detailed classification of AF which will also incorporate pathophysiological determinants and mechanisms of the arrhythmia. In turn, this will allow the development and application of precision medicine to this troublesome arrhythmia.

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Proteomics of Atrial Fibrillation

Cited by 6 publications

References 47 publications

Compartmentalisation proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation

Compartmentalisation proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation

The association between eicosanoids and incident atrial fibrillation in the Framingham Heart Study

The changing circumstance of atrial fibrillation ‐ progress towards precision medicine

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