Simon Haugaard - PhD Scholarship 2021

Project summary:
Characterising Fibrosis in Atrial Fibrillation to Discover New Treatment Targets

Atrial fibrillation (AF) is the most common sustained arrhythmia and the incidence is increasing. Various treatment options exist, but the development of heart fibrosis leads to treatment resistance and sometimes treatment failure. This research project is therefore dedicated to investigate the role of heart fibrosis in AF. Using a horse model of chronic AF, we will explore whether heart fibroblasts hold the potential to serve as a novel therapeutic target preventing AF associated heart remodeling.

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

Simon Haugaard

  • Cand.Med.Vet
  • University of Copenhagen, Department of Veterinary Clinical Sciences

Mentors:

Professor Rikke Buhl, University of Copenhagen, Department of Veterinary Clinical Sciences

Professor Stanley Nattel, University of Montreal, Montreal Heart Institute

Senior scientist Kate Herum, Novo Nordisk

Contact: