High fat diet alters left atrial electrophysiology and predisposes murine hearts to arrythmias

Tompkins, Katie ORCID: 0000-0003-4157-0387 (2025). High fat diet alters left atrial electrophysiology and predisposes murine hearts to arrythmias. University of Birmingham. M.Sc.

Preview

Tompkins2025MScbyRes.pdf
Text - Accepted Version
Available under License All rights reserved.
Download (1MB) | Preview

Abstract

Atrial fibrillation is the most common form of cardiac arrythmia. High fat diet significantly increases atrial fibrillation directly, and indirectly, through related cardiac conditions, like hypertension. High fat diet- driven electrical remodelling contributes to atrial fibrillation through ion channel alterations, inflammation, autonomic dysfunction and oxidative stress which can all lead to alterations in action potential duration, conduction velocity, diastolic interval, time to peak and more. A genetic deficiency in Pitx2 has been closely linked to atrial fibrillation, and the gene is a crucial factor for the development and function of the left atrium. A deficiency in Pitx2 can disrupt the ion channel regulation and electrical conduction, which leads to an imbalance within the electrical signalling across the atria. This creates a substrate that is prone to re-entrant circuits and ectopic activity, leading onto arrythmias.
The studies primary aim was to investigate whether a high fat diet induces electrophysiological remodelling in the murine left atria specifically, and whether the response is further modulated by altered expression of Pitx2. Additionally, the study aimed to see whether proteomic experiments can be conducted on dyed, optically mapped murine left atria.This study optically mapped the left atria only, from wild type and Pitx2 deficient mice, who both obtained a control group and a high fat diet group. Langendorff-perfused left atria were paced at different cycle lengths and recorded using optical mapping. Two-way ANOVA and one-way ANOVA statistical analyses revealed a significant difference in action potential duration, showing a prolongation in the high fat diet group against control. However, the results identified a shortening in action potential duration within the Pitx2 deficient murine hearts, versus wild type. There were no other significant differences established in the study.
The study also assessed whether optically mapped, dyed murine hearts can undergo proteomic analysis. The results found that the optically mapped hearts can successfully endure proteomic analysis, with no significant differences found between the two groups. There were a similar number of contaminants identified, all under 5 each and each heart expressed over 400 proteins.
Further experiments including a larger sample size, longer study period and using both male and female mice is essential to gain a deeper insight into the underlying mechanisms of high fat diet altering left atrial electrophysiology. Additionally, more proteomic analysis on the optically mapped, high fat diet and Pitx2 deficient hearts is crucial to conduct, to identify any metabolic changes with protein expression within the hearts.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):