scholarly journals Non‐valvular atrial fibrillation patients anticoagulated with rivaroxaban compared with warfarin exhibit reduced circulating extracellular vesicles with attenuated pro‐inflammatory protein signatures.

2021 ◽  
Author(s):  
Luisa Weiss ◽  
John Keaney ◽  
Paulina B. Szklanna ◽  
Tadhg Prendiville ◽  
Wido Uhrig ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Extracellular Vesicles ◽  
Protein Signatures ◽  
Inflammatory Protein

scholarly journals Large extracellular vesicles in the left atrial appendage in patients with atrial fibrillation—the missing link?

2021 ◽  
Author(s):  
Andreas Zietzer ◽  
Baravan Al-Kassou ◽  
Paul Jamme ◽  
Verena Rolfes ◽  
Eva Steffen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Extracellular Vesicles ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Thrombus Formation ◽  
Flow Cytometric Analysis ◽  
Heart Rhythm ◽  
Atrial Appendage ◽  
Peripheral Embolization

AbstractAtrial fibrillation (AF) is the most frequent arrhythmic disease in humans, which leads to thrombus formation in the left atrial appendage and stroke through peripheral embolization. Depending on their origin, large extracellular vesicles (lEVs) can exert pro-coagulant functions. In the present study, we investigated how different types of AF influence the levels of large EV subtypes in three distinct atrial localizations. Blood samples were collected from the right and left atrium and the left atrial appendage of 58 patients. 49% of the patients had permanent AF, 34% had non-permanent AF, and 17% had no history of AF. Flow cytometric analysis of the origin of the lEVs showed that the proportion of platelet-derived lEVs in the left atrial appendage was significantly higher in permanent AF patients compared to non-permanent AF. When we grouped patients according to their current heart rhythm, we also detected significantly higher levels of platelet-derived lEVs in the left atrial appendage (LAA) in patients with atrial fibrillation. In vitro studies revealed, that platelet activation with lipopolysaccharide (LPS) leads to higher levels of miR-222-3p and miR-223-3p in platelet-derived lEVs. Treatment with lEVs from LPS- or thrombin-activated platelets reduces the migration of endothelial cells in vitro. These results suggest that permanent atrial fibrillation is associated with increased levels of platelet-derived lEVs in the LAA, which are potentially involved in LAA thrombus formation.

Elevated blood plasma levels of tissue factor-bearing extracellular vesicles in patients with atrial fibrillation

2019 ◽  
Vol 173 ◽  
pp. 141-150 ◽  
Author(s):  
Morten Mørk ◽  
Jan J. Andreasen ◽  
Lars H. Rasmussen ◽  
Gregory Y.H. Lip ◽  
Shona Pedersen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Plasma ◽  
Tissue Factor ◽  
Extracellular Vesicles ◽  
Plasma Levels ◽  
Elevated Blood

scholarly journals Extracellular vesicles from human iPSC‐derived neural stem cells: miRNA and protein signatures, and anti‐inflammatory and neurogenic properties

2020 ◽  
Vol 9 (1) ◽  
pp. 1809064 ◽  
Author(s):  
Raghavendra Upadhya ◽  
Leelavathi N. Madhu ◽  
Sahithi Attaluri ◽  
Daniel Leite Góes Gitaí ◽  
Marisa R Pinson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Extracellular Vesicles ◽  
Protein Signatures ◽  
Anti Inflammatory ◽  
Human Ipsc

Extracellular vesicles as prospective carriers of oncogenic protein signatures in adult and paediatric brain tumours

PROTEOMICS ◽  
2013 ◽  
Vol 13 (10-11) ◽  
pp. 1595-1607 ◽  
Author(s):  
Delphine Garnier ◽  
Nada Jabado ◽  
Janusz Rak
Keyword(s):  
Extracellular Vesicles ◽  
Brain Tumours ◽  
Protein Signatures ◽  
Oncogenic Protein ◽  
Paediatric Brain Tumours

scholarly journals WHITE BLOOD CELL RESPONSE AFTER CRYOBALLOON ABLATION FOR ATRIAL FIBRILLATION IS MODIFIED BY VIRAL ANTI-INFLAMMATORY PROTEIN TREATMENT

2014 ◽  
Vol 63 (12) ◽  
pp. A462
Author(s):  
Mohammad Al-Ani ◽  
Zheng Donghang ◽  
Adisson Fortunel ◽  
Thomas Burkart ◽  
William Miles ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Cell ◽  
White Blood Cell ◽  
Cell Response ◽  
Cryoballoon Ablation ◽  
Inflammatory Protein ◽  
Anti Inflammatory ◽  
Protein Treatment

scholarly journals VIRAL ANTI-INFLAMMATORY PROTEIN TREATMENT SIGNIFICANTLY ALTERS GENE EXPRESSION IN CIRCULATING LEUKOCYTES FROM PATIENTS AFTER ATRIAL FIBRILLATION CRYOBALLOON ABLATION

2014 ◽  
Vol 63 (12) ◽  
pp. A373
Author(s):  
Adisson Fortunel ◽  
Zheng Donghang ◽  
Mohammad Al-Ani ◽  
Thomas Burkart ◽  
William Miles ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atrial Fibrillation ◽  
Cryoballoon Ablation ◽  
Inflammatory Protein ◽  
Anti Inflammatory ◽  
Protein Treatment

scholarly journals Extracellular Vesicles from Epicardial Fat Facilitate Atrial Fibrillation

Circulation ◽  
2021 ◽  
Author(s):  
Olga Shaihov-Teper ◽  
Eilon Ram ◽  
Nimer Ballan ◽  
Rafael Y. Brzezinski ◽  
Nili Naftali-Shani ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Extracellular Vesicles ◽  
Culture Medium ◽  
Heart Surgery ◽  
Biological Effects ◽  
Induced Pluripotent Stem Cell ◽  
Epicardial Fat ◽  
Human Mscs ◽  
And Migration

Background: The role of epicardial fat (eFat)-derived extracellular vesicles (EVs) in the pathogenesis of atrial fibrillation (AF) has never been studied. We tested the hypothesis that eFat-EVs transmit proinflammatory, profibrotic, and proarrhythmic molecules that induce atrial myopathy and fibrillation. Methods: We collected eFat specimens from patients with (n=32) and without AF (n=30) during elective heart surgery. eFat samples were grown as organ cultures, and the culture medium was collected every two days. We then isolated and purified eFat-EVs from the culture medium, and analyzed the EV number, size, morphology, specific markers, encapsulated cytokines, proteome, and miRNAs. Next, we evaluated the biological effects of unpurified and purified EVs on atrial mesenchymal stromal cells (MSCs) and endothelial cells (ECs) in vitro. To establish a causal association between eFat-EVs and vulnerability to AF, we modeled AF in vitro using induced pluripotent stem cell-derived cardiomyocytes (iCMs). Results: Microscopic examination revealed excessive inflammation, fibrosis, and apoptosis in fresh and cultured eFat tissues. Cultured explants from patients with AF secreted more EVs and harbored greater amounts of proinflammatory and profibrotic cytokines, as well as profibrotic miRNA, than those without AF. The proteomic analysis confirmed the distinctive profile of purified eFat-EVs from patients with AF. In vitro, purified and unpurified eFat-EVs from patients with AF had a greater effect on proliferation and migration of human MSCs and ECs, compared to eFat-EVs from patients without AF. Finally, while eFat-EVs from patients with and without AF shortened the action potential duration of iCMs, only eFat-EVs from patients with AF induced sustained reentry (rotor) in iCMs. Conclusions: We show, for the first time, a distinctive proinflammatory, profibrotic, and proarrhythmic signature of eFat-EVs from patients with AF. Our findings uncover another pathway by which eFat promotes the development of atrial myopathy and fibrillation.

scholarly journals Extracellular vesicles secreted by human cardiosphere-derived cells attenuate electrophysiological remodelling in an in vitro model of atrial fibrillation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
L Gomez-Cid ◽  
M Moro-Lopez ◽  
A S De La Nava ◽  
A I Fernandez ◽  
M E Fernandez-Santos ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Conduction Velocity ◽  
Extracellular Vesicles ◽  
In Vitro Model ◽  
Optical Mapping ◽  
Rotor Dynamics ◽  
Antiarrhythmic Effect ◽  
Electrophysiological Properties ◽  
Vitro Model

Abstract Background Stem cells and their secreted extracellular vesicles (EVs) have shown different cardioprotective effects. However, their impact on the electrophysiological properties of the heart tissue remains controversial. While the use of some progenitor cells seems to have antiarrhythmic potential, the use of cardiomyocyte-like cells may be proarrhythmic. The mechanisms behind, and whether these effects are linked to cell engraftment and not to their secreted products is not fully known. Purpose The aim of this study was to investigate the electrophysiological modifications induced by extracellular vesicles secreted by human cardiosphere-derived cells (CDC-EVs) in an in vitro model of atrial fibrillation in order to explore their potential antiarrhythmic effect. Methods CDCs were derived from cardiac biopsies of patients who underwent cardiac surgery for other reasons. Purified CDC-EVs resuspended in serum-free media (SFM) vs. SFM alone were added to HL-1 atrial myocyte monolayers presenting spontaneous fibrillatory activity. After 48 hours, the monolayers were fully confluent, and the electrophysiological properties were analysed through optical mapping in both the treated (n=9) and control plates (n=9). Optical mapping recordings of the monolayers were analysed with Matlab for the activation frequency, activation complexity, rotor dynamics (curvature and meandering) and conduction velocity. Results CDC-EVs reduced activation complexity of the fibrillating atrial monolayers by ∼40% (2.74±0.59 vs. 1.61±0.16 PS/cm2, p<0.01). This reduction in activation complexity was accompanied by larger rotor meandering (1.47±0.82 vs. 4.32±2.25 cm/s, p<0.01) and decreased curvature (1.79±0.40 vs. 0.87±0.24 rad/cm, p<0.01) in the treated group. Despite reduction in the activation complexity, activation frequency did not change significantly between both groups. This could be in part because CDC-EVs increased conduction velocity by 80% (1.32±0.57 vs. 2.65±0.87 cm/s, p<0.01). Low conduction velocity has been linked to higher reentry recurrence, and lower meandering and higher curvature to higher rotor stability and harder AF termination. Therefore, CDC-EVs seem to drive cardiomyocytes to a less arrhythmic profile reducing activation complexity and preventing remodelling by increasing conduction velocity and modifying rotor dynamics. Conclusions CDC-EVs significantly modify conduction velocity and rotor dynamics, therefore reducing fibrillation complexity and remodelling to drive atrial myocytes to a less arrhythmogenic profile. Testing CDC-EVs in more robust models of atrial fibrillation, the most common sustained arrhythmia in humans with significant morbidity and mortality, is of special interest. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III, Ministerio de Ciencia e Innovaciόn,CIBERCV, Spain Figure 1

scholarly journals Extracellular vesicles in atrial fibrillation and stroke

2020 ◽  
Vol 193 ◽  
pp. 180-189
Author(s):  
Åsa Thulin ◽  
Johan Lindbäck ◽  
Christopher B. Granger ◽  
Lars Wallentin ◽  
Lars Lind ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Extracellular Vesicles
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