Lipidomic Profiling of Atrial Fibrillation Progression in a Murine Model

Summary Atrial Fibrillation (AF) is a growing epidemic which is expected to double in prevalence by 2030. It is the most common rhythm disorder of the heart with series clinical implications, most notably stroke, where the risk can increase five-fold. Current treatments for AF have limited efficacy and/or have potentially dangerous side effects. New therapeutic targets therefore are required to address this unmet need. The area of lipidomic profiling has seen major advances due to the improvements in mass spectrometry technology in the past decade. Our lab and others have demonstrated the benefits of harnessing large scale (~800 individual lipids) lipidomic profiling in uncovering new potential therapeutic targets and/or biomarkers for the treatment/detection of various diseases, including heart failure. This study aims to comprehensively track changes in the lipidomic profile of the circulation, heart and surrounding tissues in a murine model as it develops AF.

Project Details

Atrial Fibrillation (AF) is a growing epidemic which is expected to double in prevalence by 2030. It is the most common rhythm disorder of the heart with series clinical implications, most notably stroke, where the risk can increase five-fold. Current treatments for AF have limited efficacy and/or have potentially dangerous side effects. New therapeutic targets therefore are required to address this unmet need. The area of lipidomic profiling has seen major advances due to the improvements in mass spectrometry technology in the past decade. Our laboratory and others have demonstrated the benefits of harnessing large scale (~800 individual lipids) lipidomic profiling in uncovering new potential therapeutic targets and/or biomarkers for the treatment/detection of various diseases, including heart failure. > Our laboratory has published findings demonstrating the change in specific lipids in a mouse model of AF (Nat. Comms, 2013) as well as in patients with AF (>Diabetes, 2021 < ). There is currently however a major knowledge gap as to how specific lipid species may contribute to the pathophysiology of AF.

As such, this study aims to comprehensively track changes to the Lipidomic profile of the heart and atria and Circulating lipidome through the pathological progression of AF in a mouse model. Doing so will allow us to build a clear picture of how lipids change during the progression of AF.

Key skillsets that could be obtained through this project include animal handling, exposure to echocardiography imaging and electrocardiography, molecular biology techniques such as lipid/DNA/RNA extractions and qPCR and analyses of lipidomic datasets.