scholarly journals Metabolomic and Proteomic Analyses of Persistent Valvular Atrial Fibrillation and Non-Valvular Atrial Fibrillation

2021 ◽  
Vol 12 ◽  
Author(s):  
Bo Hu ◽  
Wen Ge ◽  
Yuliang Wang ◽  
Xiaobin Zhang ◽  
Tao Li ◽  
...  

Atrial fibrillation (AF) is an abnormal heart rhythm related to an increased risk of heart failure, dementia, and stroke. The distinction between valvular and non-valvular AF remains a debate. In this study, proteomics and metabolomics were integrated to describe the dysregulated metabolites and proteins of AF patients relative to sinus rhythm (SR) patients. Totally 47 up-regulated and 41 down-regulated proteins in valvular AF, and 59 up-regulated and 149 down-regulated proteins in non-valvular AF were recognized in comparison to SR patients. Moreover, 58 up-regulated and 49 significantly down-regulated metabolites in valvular AF, and 47 up-regulated and 122 down-regulated metabolites in persistent non-valvular AF patients were identified in comparison to SR patients. Based on analysis of differential levels of metabolites and proteins, 15 up-regulated and 22 down-regulated proteins, and 13 up-regulated and 122 down-regulated metabolites in persistent non-valvular AF were identified relative to valvular AF. KEGG pathway enrichment analysis showed the altered proteins and metabolites were significantly related to multiple metabolic pathways, such as Glycolysis/Gluconeogenesis. Interestingly, the enrichment pathways related to non-valvular AF were obviously different from those in valvular AF. For example, valvular AF was significantly related to Glycolysis/Gluconeogenesis, but non-valvular AF was more related to Citrate cycle (TCA cycle). Correlation analysis between the differentially expressed proteins and metabolites was also performed. Several hub proteins with metabolites were identified in valvular AF and non-valvular AF. For example, Taurine, D-Threitol, L-Rhamnose, and DL-lactate played crucial roles in valvular AF, while Glycerol-3-phosphate dehydrogenase, Inorganic pyrophosphatase 2, Hydroxymethylglutaryl-CoAlyase, and Deoxyuridine 5-triphosphate nucleotidohydrolase were crucial in non-valvular AF. Then two hub networks were recognized as potential biomarkers, which can effectively distinguish valvular AF and non-valvular persistent AF from SR samples, with areas under curve of 0.75 and 0.707, respectively. Hence, these metabolites and proteins can be used as potential clinical molecular markers to discriminate two types of AF from SR samples. In summary, this study provides novel insights to understanding the mechanisms of AF progression and identifying novel biomarkers for prognosis of non-valvular AF and valvular AF by using metabolomics and proteomics analyses.

2020 ◽  
Vol 21 (7) ◽  
pp. 2444 ◽  
Author(s):  
Naoki Kiyosawa ◽  
Kenji Watanabe ◽  
Yoshiyuki Morishima ◽  
Takeshi Yamashita ◽  
Naoharu Yagi ◽  
...  

Novel biomarkers are desired to improve risk management for patients with atrial fibrillation (AF). We measured 179 plasma miRNAs in 83 AF patients using multiplex qRT-PCR. Plasma levels of eight (i.e., hsa-miR-22-3p, hsa-miR-128-3p, hsa-miR-130a-3p, hsa-miR-140-5p, hsa-miR-143-3p, hsa-miR-148b-3p, hsa-miR-497-5p, hsa-miR-652-3p) and three (i.e., hsa-miR-144-5p, hsa-miR-192-5p, hsa-miR-194-5p) miRNAs showed positive and negative correlations with CHA2DS2-VASc scores, respectively, which also showed negative and positive correlations with catheter ablation (CA) procedure, respectively, within the follow-up observation period up to 6-month after enrollment. These 11 miRNAs were functionally associated with TGF-β signaling and androgen signaling based on pathway enrichment analysis. Seven of possible target genes of these miRNAs, namely TGFBR1, PDGFRA, ZEB1, IGFR1, BCL2, MAPK1 and DICER1 were found to be modulated by more than four miRNAs of the eleven. Of them, TGFBR1, PDGFRA, ZEB1 and BCL2 are reported to exert pro-fibrotic functions, suggesting that dysregulations of these eleven miRNAs may reflect pro-fibrotic condition in the high-risk patients. Although highly speculative, these miRNAs may potentially serve as potential biomarkers, providing mechanistic and quantitative information for pathophysiology in daily clinical practice with AF such as possible pro-fibrotic state in left atrium, which would enhance the risk of stroke and reduce the preference for performing CA.


2020 ◽  
Vol 127 (1) ◽  
pp. 21-33 ◽  
Author(s):  
Carolina Roselli ◽  
Michiel Rienstra ◽  
Patrick T. Ellinor

Atrial fibrillation is a common heart rhythm disorder that leads to an increased risk for stroke and heart failure. Atrial fibrillation is a complex disease with both environmental and genetic risk factors that contribute to the arrhythmia. Over the last decade, rapid progress has been made in identifying the genetic basis for this common condition. In this review, we provide an overview of the primary types of genetic analyses performed for atrial fibrillation, including linkage studies, genome-wide association studies, and studies of rare coding variation. With these results in mind, we aim to highlighting the existing knowledge gaps and future directions for atrial fibrillation genetics research.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Chao-Qiang Lai ◽  
Reiko Ichikawa ◽  
Bingjie Zhou ◽  
Laurence Parnell ◽  
Sabrina Noel ◽  
...  

Abstract Objectives Sweetened beverage (SB) consumption is highly associated with obesity, but the mechanism underlying this correlation is not understood. Our objective was to examine metabolomic links between SB intake and obesity to understand metabolic mechanisms. Methods We examined the association of plasma metabolomic profiles with SB intake and obesity risk in 782 participants, aged 45–75y, in the Boston Puerto Rican Health Study (BPRHS) using linear regression models, controlling for potential confounding factors. Based on identified metabolites, we conducted pathway enrichment analysis to identify potential metabolic pathways that link SB intake and obesity risk. Genetic variants in identified metabolic pathways were examined for their interaction with SB intake on metabolites of interest and obesity. Interactions between SB and genotypes on obesity were evaluated for replication in the Framingham Heart Study (FHS). Results In BPRHS, SB intake was highly correlated with BMI (β = 0.455, P < 0.05). Among 526 measurable metabolites, 109 metabolites showed significant correlation with SB intake and 170 metabolites with BMI (P < 0.05); and 43 were correlated with both SB intake and BMI. Pathway enrichment analysis identified two metabolic pathways: phosphatidylethanolamine (PE) and lysophospholipid pathways linking SB intake and obesity, after correction for multiple testing. Focusing on the PE pathway, we identified 12 SNPs in nine genes that were significantly associated with BMI. At least four genetic variants showed suggestive interaction with SB intake on obesity risk and obesity-associated metabolites. In particular, CC carriers of rs4646360 in the PEMT (Phosphatidylethanolamine N-Methyltransferase) gene had increased risk of obesity when consuming SB. We replicated this finding in the FHS study. Conclusions We identified two key metabolic pathways linking SB intake to obesity, revealing potential mechanisms by which SB intake increases the risk of obesity. The interaction between genetic variants in the identified pathway and SB intake on obesity and obesity-associated metabolites further supports the mechanism. Funding Sources This work was funded by the US Department of Agriculture, under agreement no. 8050-51,000-098-00D, and NIH grants P01 AG023394, P50 HL105185, and R01 AG027087.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Daniela Husser ◽  
Laura Ueberham ◽  
Borislav Dinov ◽  
Jedrzej Kosiuk ◽  
Jelena Kornej ◽  
...  

2021 ◽  
pp. 204589402110543
Author(s):  
Samar Farha ◽  
Suzy Comhair ◽  
Yuan Hou ◽  
Margaret Park ◽  
Jacqueline Sharp ◽  
...  

Alterations in metabolism and bioenergetics are hypothesized in the mechanisms leading to pulmonary vascular remodeling and heart failure in pulmonary hypertension (PH). To test this, we performed metabolomic analyses on 30 PH individuals and 12 controls. Furthermore, using 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), we dichotomized PH patients into metabolic phenotypes of high and low right ventricle (RV) glucose uptake and followed them longitudinally. In support of metabolic alterations in PH and its progression, the high RV glucose group had higher RVSP (p < 0.001), worse RV function as measured by RV fractional area change and peak global longitudinal strain (both p < 0.05) and may be associated with poorer outcomes (33% death or transplantation in the high glucose RV uptake group compared to 7% in the low RV glucose uptake group at 5 years follow up, log-ranked p = 0.07). Pathway enrichment analysis identified key metabolic pathways including fructose catabolism, arginine-nitric oxide metabolism, tricarboxylic acid (TCA) cycle, and ketones metabolism. Integrative human protein-protein interactome network analysis of metabolomic and transcriptomic data identified key pathobiological pathways: arginine biosynthesis, TCA cycle, purine metabolism, hypoxia-inducible factor 1 and apelin signaling. These findings identify a PH metabolomic endophenotype, and for the first time link this to disease severity and outcomes.


2020 ◽  
Vol 138 ◽  
pp. 227-235 ◽  
Author(s):  
Y Li ◽  
W Xu ◽  
X Li ◽  
Z Han ◽  
R Zhang ◽  
...  

Tachaea chinensis, a parasitic isopod, negatively affects the production of several commercially important shrimp species in China. The mechanism of parasite-host interaction cannot be accurately described by transcriptomic and proteomic approaches individually. Here, comparative metabolite profiling was used to achieve a broad coverage of primary metabolite changes in Chinese grass shrimp Palaemonetes sinensis following T. chinensis parasitization. In total, 66 metabolites were significantly differentially accumulated between the control and infected groups; of these, 19 were upregulated and 47 were downregulated after T. chinensis infection. Moreover, the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that 10 pathways were significantly enriched. The protein digestion and absorption pathways were highly enriched, followed by the mineral absorption, aminoacyl-tRNA biosynthesis, biosynthesis of amino acids, and metabolic metabolism pathways. Parasitization by T. chinensis enhanced the glycolytic pathway and tricarboxylic acid (TCA) cycle in P. sinensis, thereby releasing more energy for swimming, foraging, and evading predation. Glucogenic amino acids such as alanine, histidine, glutamine, and proline were consumed to generate glutamate and enhance the TCA cycle. Nucleotide-related metabolic pathways were downregulated, possibly because T. chinensis can secrete molecules to degrade nucleotides and inhibit hemostasis and inflammatory responses. These results suggest that the isopod parasite can increase the host’s metabolic burden by enhancing the host’s TCA cycle and secreting molecules to degrade host proteins, thereby enabling the parasite to feed on the host and inhibit an inflammatory response. The results will be a valuable contribution to understanding the metabolic responses of crustaceans to isopod parasitism.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yahong Sun ◽  
Gang Chen ◽  
Zhihao Liu ◽  
Lina Yu ◽  
Yan Shang

Abstract Background Due to the fact that pulmonary tuberculosis (PTB) is a highly infectious respiratory disease characterized by high herd susceptibility and hard to be treated, this study aimed to search novel effective biomarkers to improve the prognosis and treatment of PTB patients. Methods Firstly, bioinformatics analysis was performed to identify PTB-related differentially expressed genes (DEGs) from GEO database, which were then subjected to GO annotation and KEGG pathway enrichment analysis to initially describe their functions. Afterwards, clustering analysis was conducted to identify PTB-related gene clusters and relevant PPI networks were established using the STRING database. Results Based on the further differential and clustering analyses, 10 DEGs decreased during PTB development were identified and considered as candidate hub genes. Besides, we retrospectively analyzed some relevant studies and found that 7 genes (CCL20, PTGS2, ICAM1, TIMP1, MMP9, CXCL8 and IL6) presented an intimate correlation with PTB development and had the potential serving as biomarkers. Conclusions Overall, this study provides a theoretical basis for research on novel biomarkers of PTB, and helps to estimate PTB prognosis as well as probe into targeted molecular treatment.


10.36469/9797 ◽  
2017 ◽  
Vol 5 (1) ◽  
pp. 39-54
Author(s):  
Yazid Aoudia ◽  
Thitima Kongnakorn ◽  
Evie Merinopoulou ◽  
Mohamed Said Bettayeb ◽  
Sid Ahmed Kherraf

Background: Atrial fibrillation (AF) is a chronic sustained heart rhythm disorder associated with an increased risk of stroke. Apixaban, a new oral anticoagulant, was approved by the European Medicines Agency for prevention of stroke in patients with AF. The efficacy of apixaban has been investigated in randomised controlled trials. Objectives: The objective of this study was to estimate the economic implications of using apixaban compared to other anti-coagulations to reduce the risk of stroke in patients with AF from the perspective of the Algerian payer. Methods: A previously published Markov model was adapted to the Algerian setting. The model included patients for whom vitamin K antagonist (VKA) treatment is suitable and could initiate on acenocoumarol, rivaroxaban or apixaban, and those unsuitable for VKA treatment who could initiate on aspirin or apixaban. Over a lifetime time horizon, costs were estimated in Algerian dinars (DZD) and outcomes included life-years (LYs), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Results: In the VKA suitable population, apixaban was estimated to be a dominant treatment option over rivaroxaban, providing a higher number of QALYs at lower costs, while when compared with acenocoumarol, an ICER of 3 672 059 DZD per QALY gained was estimated. Amongst those unsuitable for VKA therapy, the ICER was 2 061 863 DZD per QALY gained. Conclusion: Apixaban was found to be a cost-effective choice for stroke prevention in patients with AF in Algeria compared to acenocoumarol and rivaroxaban in the VKA suitable population and compared to aspirin in the VKA unsuitable population.


2018 ◽  
Vol 13 (SP1) ◽  
Author(s):  
Jeff Healey

Stroke due to atrial fibrillation (AF) is common, the cause of significant morbidity and mortality, but is highly preventable with the appropriate use of oral anticoagulants. Recent advances in implantable and wearable electrocardiographic (ECG) technologies now allow continuous monitoring of a patient’s heart rhythm for months or years at a time.  Cohort studies have shown that using such methods, it is very common to find asymptomatic, short-lasting episodes of subclinical AF. Subclinical AF is also associated with an increased risk of stroke; however, the risk is lower than with traditional, ECG-detected AF and the absolute risk appears to depend on the overall burden of AF.  There is currently great uncertainty as to what duration of AF should trigger the use of oral anticoagulation in specific patient groups. Large randomized trials are underway to help clarify this issue; however, in the meantime, researchers and guideline committees have proposed some guidance to assist clinicians.


2020 ◽  
Vol 17 (2) ◽  
pp. 202
Author(s):  
ERIC HARTONO TEDYANTO ◽  
KEN CHRISTIAN KAWILARANG ◽  
FEISAL TANJUNG

<p><strong>ABSTRACT</strong></p><p><strong>Background: </strong>Stroke is the leading cause of disability and the second most common cause of death in the world. Atrial fibrillation (AF) is the major risk factor for embolic stroke. Patients with atrial fibrillation have a 5 times much more risk of stroke to those who do not have atrial fibrillation.</p><p><strong>Case Report: </strong>A 40-year-old woman came to the Emergency Unit with chief complaints the left-sided limbs suddenly weakened while cooking. On ECG examination there is an irregular rhythm (irregular P-P), leading to an atrial fibrillation. CT scan revealed hypodense lesions on the temporal part of the left side, leading to a cerebral infarction.</p><p><strong>Discussion:</strong> AF puts patients at an increased risk for stroke because blood can ot be properly pumped, which caused stagnation and formed a blood clot. This clot can released from ventricle, then travel to the other organ via artery, including brain and block the blood flow which can result a infarct stroke.<strong> </strong></p><p><strong>Conclusion: </strong>Close supervision and routine control are needed for patients with heart rhythm disorders, especially atrial fibrillation to prevent embolic stroke.</p><p><strong>Keywords: </strong>embolic stroke, atrial fibrilation.</p><p><strong>ABSTRAK</strong></p><p><strong>Latar Belakang:</strong> Stroke adalah penyebab utama kecacatan dan penyebab kematian paling umum kedua di dunia. Fibrilasi atrium (AF) secara numerik merupakan faktor risiko paling penting untuk stroke. Sudah dipastikan bahwa pasien dengan AF memiliki risiko stroke 5 kali lipat relatif terhadap mereka yang tidak.</p><p><strong>Laporan Kasus: </strong>Seorang perempuan 40 tahun datang ke IGD dengan keluhan anggota gerak sisi kiri secara tiba-tiba melemah saat sedang memasak. Pada pemeriksaan EKG didapatkan adanya irama ireguler (P-P ireguler), mengarah ke suatu fibrilasi atrium. Pada pemeriksaan CT Scan didapatkan adanya lesi hipodense di bagian temporal sisi kiri, mengarah ke suatu infark serebri.</p><p><strong>Diskusi:</strong> AF merupakan faktor resiko tinggi untuk stroke karena darah mungkin tidak dipompa dengan baik dari jantung, yang dapat menyebabkannya mengumpul dan membentuk gumpalan di dalam ventrikel. Gumpalan ini kemudian dapat lepas dan mengalir ke otak dan memblokir aliran darah ke bagian otak yang dapat menyebabkan stroke.</p><p><strong>Kesimpulan:</strong> Pengawasan ketat dan kontrol yang rutin sangat diperlukan bagi pasien penderita gangguan irama jantung khususnya fibrilasi atrium untuk mencegah terjadinya stroke emboli.</p><p><strong>Kata Kunci</strong>: stroke emboli, fibrilasi atrium</p>


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