Towards a greater understanding of Atrial Fibrillation: Proteomics and genomics of a common global cardiac rhythm disorder

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Heart disease is the leading cause of global morbidity and mortality with numbers continually increasing as the global population ages. Atrial fibrillation (AF) is the most common heart rhythm disorder in the world effecting between 1-2% of the general global population, leading to a major public health impact, especially due to increased risk of stroke and hospitalizations. Cardiac remodelling arising from altered protein expression results in electrical, contractile and structural changes leading to an altered heart rhythm in patients which can be progressive in a large number of patients. The severity of AF ranges from paroxysmal AF which is self-terminating (usually within 48 h) to longstanding persistent AF (where the arrhythmia has lasted for 1 year or more in which a rhythm control strategy is used normally via catheter ablation) through to permanent AF (when the presence of the arrhythmia is constant). In this project we aim to understand the differences in the multiple sub-types of AF as a means of understanding individual manifestations as well as progression of disease and the ageing process. This project will use human patient samples, and compare protein and genetic differences between paroxysmal, persistent and permanent AF. Since AF is known to progress in severity over the ageing process we will further use animal models of AF to monitor functional and structural changes over time. Taken together we aim to identify changes at the molecular, cellular and physiological levels that lead to an increased risk of AF. We will use high-end proteomics and genomics to identify pathways and biomarkers involved in disease. Once differentially expressed proteins have been identified we will investigate these further using in vitro 2D and 3D cardiac systems established within our group. Catheter ablation is a frequently used treatment method for the restoration of normal heart rhythm in AF patients. This project will further compare samples pre- and post-ablation to see how rhythm management alters the protein profile in patients.