PhD ceremony Ms. A.R. de Jong: New insights in atrial remodeling

PhD ceremony: Ms. A.R. de Jong

Dissertation: New insights in atrial remodeling

Promotor(s): prof. I.C. van Gelder, prof. W.H. van Gilst

Faculty: Medical Sciences

Atrial fibrillation is the most common cardiac arrhythmia. Risk factors for atrial fibrillation include older age, hypertension, diabetes, valve disease and heart failure. During atrial fibrillation atrial remodeling takes place. Atrial remodeling refers to changes in the atria, including structural changes such as an increase in atrial size. These structural changes are also caused by underlying diseases such as hypertension and heart failure. The aim of this thesis was to investigate this atrial remodeling.

The focus is on remodeling caused by stretch (mimicking these underlying diseases) and by activated coagulation factors. First, different aspects of structural atrial remodeling are reviewed with a special focus on stretch and its contribution to structural remodeling. Next we investigated the effects of stretch in a cell model; therefore neonatal rat atrial myocytes were subjected to cyclical stretch. To translate the findings to an animal model we used a model in which the aorta is constricted. This aortic constriction leads to increased stress on the heart and results in so called ventricular hypertrophy, i.e. in a large ventricle. In this model the structural changes in the atria were studied. In addition to known factors involved in remodeling also previously unknown factors might be involved in the remodeling process. One such factor might be activated coagulation.

In this thesis the effects of the activated coagulation factors thrombin and factor Xa on cellular processes in both atherosclerosis and atrial fibrillation are reviewed. In addition, the effects of thrombin on atrial fibroblasts and remodeling are studied.