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Large extracellular vesicles in the left atrial appendage in patients with atrial fibrillation-the missing link?

ABSTRACT: Atrial 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.

SUBMITTER: Zietzer A

PROVIDER: S-EPMC8766378 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSurgical left atrial appendage occlusion (SLAAO) may be associated with a lower risk of thromboembolism in patients with atrial fibrillation undergoing cardiac surgery. However, evidence regarding the effectiveness of SLAAO in patients undergoing mechanical heart valve replacement (MHVR) is lacking. Therefore, we aimed to evaluate the association between SLAAO and the cardiovascular outcomes in patients with atrial fibrillation undergoing MHVR.MethodsWe retrospectively analyzed data for 497 patients with atrial fibrillation; 27.6% of the patients underwent SLAAO, and the remainder of the patients did not (No-SLAAO group). The primary outcome was a composite of ischemic stroke, systemic embolism, and all-cause mortality. Cumulative event-free survival rates were estimated using Kaplan-Meier curves, and we performed multivariate Cox analyses to evaluate the association between SLAAO and outcomes. We used one-to-one propensity score matching to balance patients' baseline characteristics, and analyzed 120 matching pairs.ResultsFive patients died within 30 days postoperatively, and there were no significant differences between the two groups regarding in-hospital complications (all P > 0.05). After a median follow-up of 14 months, 14 primary events occurred. Kaplan-Meier curves showed no difference in the cumulative incidence of freedom from the primary outcome (log-rank P = 0.830), hemorrhagic events (log-rank P = 0.870), and the secondary outcome (log-rank P = 0.730), between the two groups. Multivariable Cox proportional hazards regression analysis showed no association between SLAAO and any outcome (all P > 0.05). After propensity score matching, cardiopulmonary bypass time and aortic cross-clamp time, and the postoperative length of stay were significantly longer in the SLAAO group (all P < 0.05); results were similar to the unadjusted analyses.ConclusionsConcomitant SLAAO and MHVR was associated with longer length of stay, and cardiopulmonary bypass time and aortic cross-clamp time, but was not associated with additional protective effects against thromboembolic events and mortality during the 14-month follow-up.

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Large extracellular vesicles in the left atrial appendage in patients with atrial fibrillation-the missing link?

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