Project Title

Investigating the Role of Fibroblast Activation in Atrial Fibrillation Pathophysiology

Background

AF is a progressive disease that over time develops into more persistent forms due to heart remodeling. Key players are the highly abundant fibroblasts that upon stimuli activates and produces fibrosis. Prevention of fibrosis could serve as a novel treatment approach, but knowledge on the structural remodelling during AF is limited. The horse model of AF provides us with a unique opportunity to yield a detailed and up until now unavailable characterisation of the structural remodelling of the heart during AF.

Aim

The aim of this research project is to investigate how one of the most abundant types of cells in the heart, namely the fibroblasts, are involved in the pathogenesis of AF. Furthermore, the project will investigate whether metformin treatment inhibits the activation of fibroblasts and decreases fibrosis formation during AF.

Methods

The study will include 20 retired trotting horse that will be tachypaced into AF. Half of the horses will receive metformin treatment; the other half receive a placebo. Atrial tissue biopsies will be sampled at several fixed time points over a 4-month period. We will apply various cellular and molecular techniques to characterise the atrial remodelling during AF, including:

• Immunohistochemistry and histology
• RNA-sequencing
• Isolation and in-vitro activation of fibroblasts
• Mitochondrial activity analysis