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Uncovering novel mechanosensing pathways that underlie cardiac arrhythmias

Victor Chang Cardiac Research Institute

  • Early-Mid Career Fellowship
Date Funded:
  • 31 May, 2018
Chief Investigator/s:
  • Dr. Charles David Cox

Atrial fibrillation (AF), the most common abnormal heart rhythm (arrhythmia), is a major risk factor for both stroke and heart failure. With an ageing population tackling the problem of arrhythmias, in particular AF, will be a major challenge for healthcare in the coming decades. At present, we lack good drugs to treat AF. As a result there is a pressing need for new strategies to study and better understand the molecular basis of these arrhythmias. This is the best way to identify and develop novel therapeutic avenues.

While clinically we accept that altered mechanical load in the chambers of the heart leads to structural and electrical changes, the molecular mechanisms of how these mechanical forces underpin arrhythmias are not understood. This project aims to identify novel mechanical pathways that underlie arrhythmias in conditions like AF.

This project will identify these new cellular pathways underlying arrhythmia generation by evaluating how mechanical stress affects the cells that line the chambers of the heart. We have access to a unique cell type mimicking the single cell layer that lines the inner wall of the heart chambers. Using state-of-the-art technology to simulate blood flow this project will assess how these cells may provide mechanically-regulated signals to the underlying heart muscle cells and assess how this may contribute to arrhythmias. This crucially acknowledges the inseparable function of the specialized cells that line the heart chambers and the muscle cells in the overall performance of the heart. Understanding these molecular pathways and their effect on the underlying heart muscle will likely identify novel therapeutic targets for prevention but also for management of arrhythmias.

Aside from unearthing targets for therapy, these pathways are also likely to contain candidate genes for genetic studies in patients with inherited heart arrhythmias and atrial fibrillation. Thus data generated in this study will be used to look for disease causing gene variants in studies already ongoing such as a NSW Health funded project aimed at sequencing the genomes of a large cohort of patients with cardiomyopathies, many of whom will develop AF and associated arrhythmias. As a result this project is likely to provide tangible outcomes for patient and family management and counselling.