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Investigating the role of enhanced NLRP3 inflammasome activation in atrial fibrillation

Carlsbergfondets internationaliseringsstipendier

What

Atrial fibrillation is the most common heart rhythm disorder worldwide. An enhanced inflammatory response is commonly observed in patients with atrial fibrillation and increased levels of circulating pro-inflammatory cytokines are found to positively correlated with the progression of the disease. The NLRP3 inflammasome is a key inflammatory signalling complex that regulates innate immunity and serves as an inflammatory signalling-amplifier regulating the release of pro-inflammatory cytokines. Recent studies demonstrated that the activity of the NLRP3 inflammasome is increased in patients with a history of atrial fibrillation. However, the precise role of NLRP3 inflammasome activation and signalling in atrial fibrillation pathogenesis remains elusive.

Why

Despite the high prevalence of atrial fibrillation, the available treatment strategies are inadequate and there is a need for safer and more efficacious treatment options. The most prominent explanation for the lack of new medicine is the high number of factors promoting atrial fibrillation as well as a limited understanding of this complex disease and its progression. The overall aim of this research project is to establish how the inflammatory signalling complex, the NLRP3 inflammasome, is involved in the pathogenesis of atrial fibrillation.

How

The work outlined in this project will be conducted in Prof. Dobromir Dobrev's laboratory at the Institute of Pharmacology, University of Duisburg-Essen, Germany. Prior to initiating this project at University of Duisburg-Essen, I will, in collaboration with Prof. Thomas Jespersen's team at the University of Copenhagen generate a tachypacing-induced large animal model of atrial fibrillation, which will enable me to use these heart samples during my two-year postdoctoral stay at University of Duisburg-Essen.

SSR

Atrial fibrillation is the most common heart rhythm disorder worldwide affecting more than 33.5 million and associated with significant morbidity and mortality. The growing prevalence of atrial fibrillation is increasing the burden on the public health care systems worldwide, why current treatment options need to be improved. With this fellowship, I will deliver important novel insights, facilitating development of a new, safe and effective therapeutic treatment regimens for atrial fibrillation patients.