Noortje Noortje Bax

The epicardium as modulator of the cardiac autonomic response during early development

The cardiac autonomic nervous system (cANS) modulates heart rate, contraction force and conduction velocity. The embryonic chicken heart already responds to epinephrine prior to establishment of the cANS. The aim of this study was to define the regions of the heart that might participate in modulating the early autonomic response to epinephrine. Immunofluorescence analysis reveals expression of neural markers tubulin beta-3 chain and neural cell adhesion molecule in the epicardium during early development. In addition, expression of the β2 adrenergic receptor, the receptor for epinephrine, was found in the epicardium. Ex-ovo micro-electrode recordings in hearts with inhibition of epicardial outgrowth showed a significantly reduced response of the heart rate to epinephrine compared to control hearts. This study suggests a role for the epicardium as autonomic modulator during early cardiac development.

Developing Engineered Cardiac Tissue Models from HL-1 Cardiomyocytes and Mouse Embryonic Fibroblasts

Engineered cardiac tissue models become increasingly important for understanding normal and diseased cardiac physiology. The use of in-vitro engineered disease models can give more insight in the changing structure-function properties during pathological condition; therefore, contributing to the development of new cardiac therapies. It is hypothesized that during cardiac disorders of impaired mechanotransduction, the ratios of cardiomyocytes, fibroblasts and their supporting endogenous extracellular matrix (ECM) change. Furthermore, these changes are comparable and predictable of the different stages of diseased cardiac tissue. The aim of this study is to investigate the effect of different cardiomyocyte/fibroblast ratios on tissue morphology and function. Co-cultures of the HL-1 cardiomyocyte cell line and mouse embryonic fibroblasts (MEFs) at different ratios were used in 2D feasibility studies. Cyclic mechanical straining was applied to mimic cardiac tissue deformation during contraction. Both HL-1 and MEFs survived in co-culture although clustering of HL-1 cells was observed. The cluster size of HL-1 was dependent on the amount of MEFs. Mechanical stimulation of cultures showed strain avoidance response of MEFs while co-culture with HL-1 prevented this response. The data obtained provides new insights in the usefulness of cardiac cell-line-derived HL-1 and MEFs in the development of cardiac tissue models.