Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA039

Poster Communications

Cardiosphere-derived cells as a Model System for Myocardial Infarction

L. Salhöfer1, J. Fandrey1, T. Schreiber1

1. Institute of Physiology, University of Duisburg-Essen, Essen, Germany.

Coronary heart disease is the most common cause of death in Europe1. Although tremendous achievements were made in prevention and treatment of myocardial infarction the resulting fibrotic scar remains a major threat. Ischemia and reperfusion (I/R) of the myocardium has to be thoroughly studied on a molecular basis to discover and understand new targets to treat I/R injury. The experiments to unveil new targets were performed with cardiosphere-derived cells (CDCs). CDCs are a heterogenous primary cell culture created from murine neonatal hearts2 containing cardiomyocytes, endothelial cells, smooth muscle cells and stem cells3. In order to simulate myocardial infarction, oxygen-glucose deprivation (OGD; 0.2% O2, glucose-free medium) was performed for several periods of time (1h, 2h, 4h, 6h, 8h) followed by one hour of reperfusion with oxygen and glucose. Additionally, the response to hypoxia alone was studied by exposing the cells to hypoxia (1% O2) for 24h, 48h, and 72h with a normoxic control to investigate the impact of hypoxia-inducible factor stabilization in the cells. Because exposure to low oxygen and lack of glucose is a tough challenge we presume that the CDCs metabolism and ultrastructure will suffer under OGD. First results showed significant changes in mRNA expression of various genes. Among these, we observed a significant down regulation of connexin 43 (Cx43), a substantial part of the myocardial gap junction. This might impact myocardial conduction and lead to arrhythmia, a common complication after ischemic heart injury. Furthermore, the expression of Adra1b (alpha-1b adrenergic receptor) and Adra1d (alpha-1d adrenergic receptor) were significantly decreased, suggesting that the challenge has a negative impact on the mitotic capability of CDCs. Cx43 and the alpha adrenergic receptors are only two possible examples to tackle complications after I/R injury. It is important to further investigate these and other possible targets to improve the long-term outcome of myocardial infarction.

Where applicable, experiments conform with Society ethical requirements