Abstract 3490: Mechanistic Involvement of Myeloperoxidase in the Pathogenesis of Atrial Fibrillation

Autor: Volker Rudolph, Rene Andrie, Kai Friedrichs, Tanja K Rudolph, Anna Klinke, Denise Lau, Katalin Scoecs, Jan Schrickel, Thorsten Lewalter, Georg Nickenig, Thomas Meinertz, Stephan Willems, Stephan Baldus
Rok vydání: 2008
Předmět:
Zdroj: Circulation. 118
ISSN: 1524-4539
0009-7322
DOI: 10.1161/circ.118.suppl_18.s_434-c
Popis: Background: Observational clinical and ex-vivo studies have established a strong association between atrial fibrillation (AF) and inflammation. However, whether inflammation is cause or consequence of AF and which specific inflammatory mediators increase atrial susceptibility to fibrillate remain elusive. Herein, we provide evidence for mechanistic involvement of myeloperoxidase (MPO), a heme enzyme abundantly expressed by neutrophils, in the pathophysiology of AF. Methods and Results: Patients with AF assessed by pacemaker interrogation not only exhibited higher circulating plasma levels of MPO (503.1 [IR:404.6 –880.7] vs. 437.8 [IR:348.9 – 488.0 pmol/l; p=0.03; n=42), they also revealed an increased MPO burden in explanted left atrial tissue as compared to patients devoid of AF. In AF-patients MPO co-localized with markedly increased formation of 3-nitro and 3-chlorotyrosin, protein oxidations known to be catalyzed by MPO. Myeloperoxidase knock-out mice, pretreated with angiotensin II infusion for 2 weeks yielding increased neutrophil activation, revealed strikingly attenuated vulnerability for AF during right atrial electrophysiological stimulation as compared to wild type mice (probability of AF-induction: 3.0 vs. 12.7%; p Conclusion: In conclusion, the current findings not only underscore the significance of neutrophil activation as a critical pathophysiological prerequisite of AF, but reveal that MPO - by oxidatively modifying protein residues and increasing fibrosis of atrial myocytes - is causally linked to the initiation and perpetuation of AF.
Databáze: OpenAIRE
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