Combinational Biomarkers for Atrial Fibrillation Derived from Atrial Appendage and Plasma Metabolomics Analysis

Lai, Songqing; Hua, Xiumeng; Gao, Ran; Zeng, Liang; Song, Jiangping; Liu, Jichun; Zhang, Jing

doi:10.1038/s41598-018-34930-6

Cited by 25 publications

(17 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The PREDIMED cohort reported positive associations between plasma choline and increased risk of major cardiovascular events [74]. In a recent cross-sectional study of 49 atrial fibrillation (AF) patients, plasma choline concentrations were higher than normal [75]. Results from 3 prospective cohort studies are also consistent with respect to the association between plasma choline and AF incidence [76].…”

Section: Where Does Tmao Come From?mentioning

confidence: 87%

Trimethylamine N-Oxide in Relation to Cardiometabolic Health—Cause or Effect?

2020

View full text Add to dashboard Cite

Trimethylamine-N-oxide (TMAO) is generated in a microbial-mammalian co-metabolic pathway mainly from the digestion of meat-containing food and dietary quaternary amines such as phosphatidylcholine, choline, betaine, or L-carnitine. Fish intake provides a direct significant source of TMAO. Human observational studies previously reported a positive relationship between plasma TMAO concentrations and cardiometabolic diseases. Discrepancies and inconsistencies of recent investigations and previous studies questioned the role of TMAO in these diseases. Several animal studies reported neutral or even beneficial effects of TMAO or its precursors in cardiovascular disease model systems, supporting the clinically proven beneficial effects of its precursor, L-carnitine, or a sea-food rich diet (naturally containing TMAO) on cardiometabolic health. In this review, we summarize recent preclinical and epidemiological evidence on the effects of TMAO, in order to shed some light on the role of TMAO in cardiometabolic diseases, particularly as related to the microbiome.

show abstract

Section: Where Does Tmao Come From?mentioning

confidence: 87%

Trimethylamine N-Oxide in Relation to Cardiometabolic Health—Cause or Effect?

2020

View full text Add to dashboard Cite

show abstract

“…There have been a few small-scale studies comparing the metabolomics profile of patients with prevalent AF with that of controls without AF. 27,28 However, because patients with AF most often receive medications with possible effects on the metabolome, such studies are hard to interpret.…”

Section: Comparison With the Literaturementioning

confidence: 99%

Multicohort Metabolomics Analysis Discloses 9‐Decenoylcarnitine to Be Associated With Incident Atrial Fibrillation

Lind

Salihović

Sundström

et al. 2021

JAHA

View full text Add to dashboard Cite

Background The molecular mechanisms involved in atrial fibrillation are not well known. We used plasma metabolomics to investigate if we could identify novel biomarkers and pathophysiological pathways of incident atrial fibrillation. Methods and Results We identified 200 endogenous metabolites in plasma/serum by nontargeted ultra‐performance liquid chromatography coupled to time‐of‐flight mass spectrometry in 3 independent population‐based samples (TwinGene, n=1935, mean age 68, 43% females; PIVUS [Prospective Investigation of the Vasculature in Uppsala Seniors], n=897, mean age 70, 51% females; and ULSAM [Uppsala Longitudinal Study of Adult Men], n=1118, mean age 71, all males), with available data on incident atrial fibrillation during 10 to 12 years of follow‐up. A meta‐analysis of ULSAM and PIVUS was used as a discovery sample and TwinGene was used for validation. In PIVUS, we also investigated associations between metabolites of interest and echocardiographic indices of myocardial geometry and function. Genome‐wide association studies were performed in all 3 cohorts for metabolites of interest. In the meta‐analysis of PIVUS and ULSAM with 430 incident cases, 4 metabolites were associated with incident atrial fibrillation at a false discovery rate <5%. Of those, only 9‐decenoylcarnitine was associated with incident atrial fibrillation and replicated in the TwinGene sample (288 cases) following adjustment for traditional risk factors (hazard ratio, 1.24 per unit; 95% CI, 1.06–1.45, P =0.0061). A meta‐analysis of all 3 cohorts disclosed another 4 significant metabolites. In PIVUS, 9‐decenoylcarnitine was related to left atrium size and left ventricular mass. A Mendelian randomization analysis did not suggest a causal role of 9‐decenoylcarnitine in atrial fibrillation. Conclusions A nontargeted metabolomics analysis disclosed 1 novel replicated biomarker for atrial fibrillation, 9‐Decenoylcarnitine, but this acetylcarnitine is likely not causally related to atrial fibrillation.

show abstract

“… 45 Glutamate was also found to be significantly increased in AF patient left atrial appendages. 46 Glutamate signaling is important in vagal afferent neurons, 47 and remodeling of the glutamate system in AF may relate to the extensive previous evidence of autonomic dysfunction in patients with AF. 48 Moreover, a recent study has shown fundamental roles for glutamatergic receptors in rat atrial cardiomyocytes and induced pluripotent stem cell-derived atrial cardiomyocytes, including a reduction in cardiomyocyte excitability after GRIA3 knockdown.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Profiling of Canine Atrial Fibrillation Models After One Week of Sustained Arrhythmia

Leblanc

Hassani

Liesinger

et al. 2021

Circ: Arrhythmia and Electrophysiology

View full text Add to dashboard Cite

Background - Atrial fibrillation (AF), the most common sustained arrhythmia, is associated with increased morbidity, mortality, and health-care costs. AF develops over many years and is often related to substantial atrial structural and electrophysiological remodeling. AF may lack symptoms at onset and atrial biopsy samples are generally obtained in subjects with advanced disease, so it is difficult to study earlier-stage pathophysiology in humans. Methods - Here, we characterized comprehensively the transcriptomic (miRNAseq and mRNAseq) changes in the left atria of two robust canine AF-models after one week of electrically-maintained AF, without or with ventricular rate-control via atrioventricular node-ablation/ventricular pacing. Results - Our RNA-sequencing experiments identified thousands of genes that are differentially expressed, including a majority that have never before been implicated in AF. Gene-set enrichment analyses highlighted known (e.g. extracellular matrix structure organization) but also many novel pathways (e.g. muscle structure development, striated muscle cell differentiation) that may play a role in tissue remodeling and/or cellular trans-differentiation. Of interest, we found dysregulation of a cluster of non-coding RNAs, including many microRNAs but also the MEG3 long non-coding RNA orthologue, located in the syntenic region of the imprinted human DLK1-DIO3 locus. Interestingly (in the light of other recent observations), our analysis identified gene-targets of differentially expressed microRNAs at the DLK1-DIO3 locus implicating glutamate signaling in AF pathophysiology. Conclusions - Our results capture molecular events that occur at an early stage of disease development using well-characterized animal models, and may therefore inform future studies that aim to further dissect the causes of AF in humans.

show abstract

Combinational Biomarkers for Atrial Fibrillation Derived from Atrial Appendage and Plasma Metabolomics Analysis

Cited by 25 publications

References 46 publications

Trimethylamine N-Oxide in Relation to Cardiometabolic Health—Cause or Effect?

Trimethylamine N-Oxide in Relation to Cardiometabolic Health—Cause or Effect?

Multicohort Metabolomics Analysis Discloses 9‐Decenoylcarnitine to Be Associated With Incident Atrial Fibrillation

Transcriptomic Profiling of Canine Atrial Fibrillation Models After One Week of Sustained Arrhythmia

Contact Info

Product

Resources

About