The epicardium is embryologically formed by outgrowth of proepicardial cells over the naked heart tube. Epicardium-derived cells (EPDCs) migrate into the myocardium, contributing to myocardial architecture, valve development, and the coronary vasculature. Defective EPDC formation causes valve malformations, myocardial thinning, and coronary defects. In the atrioventricular (AV) valves and the fibrous heart skeleton isolating atrial from ventricular myocardium, EPDCs colocalize with periostin, a matrix molecule involved in remodeling. We investigated whether proepicardial outgrowth inhibition affected periostin expression and how this related to development of the AV valves and fibrous heart skeleton. Periostin expression by epicardium and EPDCs was confirmed in vitro in primary cultures of human and quail EPDCs. Disturbing EPDC formation in quail embryos reduced periostin expression in the endocardial cushions and AV junction. Disturbed fibrous tissue development resulted in AV myocardial connections reflected by preexcitation electrocardiographic patterns. We conclude that EPDCs are local producers of periostin. Disturbance of EPDC formation results in decreased cardiac periostin levels and hampers the development of fibrous tissue in AV junction and the developing AV valves. The resulting cardiac anomalies might link to Wolff-Parkinson White syndrome with persistent AV myocardial connections.

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Keywords Atrioventricular junction, Epicardium-derived cells, Heart development, Periostin, Valve
Persistent URL dx.doi.org/10.1111/j.1432-0436.2007.00262.x, hdl.handle.net/1765/29741
Citation
Lie-Venema, H., Eralp, I., Markwald, R.R., van den Akker, N.M.S., Wijffels, M.C.E.F., Kolditz, D.P., … Gittenberger-De Groot, A.C.. (2008). Periostin expression by epicardium-derived cells is involved in the development of the atrioventricular valves and fibrous heart skeleton. Differentiation, 76(7), 809–819. doi:10.1111/j.1432-0436.2007.00262.x