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Acta Physiologica 2013; Volume 207, Supplement 694
92nd Annual Meeting of the German Physiological Society
3/2/2013-3/5/2013
Heidelberg, Germany
PPAR-GAMMA CONTROLS THE CARDIOVASCULAR DIFFERENTIATION IN EMBRYONIC STEM CELLS IN VITRO
Abstract number: P029
Danzer
1
C.
, El Saied
1
M., Finkensieper
1
A., P顤ner
1
T., Figulla
1
H.-R., Sauer
1
H., Wartenberg
1
*M.
1
Universit酹sklinikum Jena, KIM I, Jena, Germany
Question:
The expression of peroxisome proliferator activated receptors (PPARs) in embryonic stem (ES) cells follows a detailed time schedule during differentiation. PPAR-gamma and delta are upregulated starting from day 4 and reach a maximum of mRNA expression between day 6 and day 8. Subsequently PPAR-gamma/ delta are down regulated. PPAR-alpha is upregulated from day 8 of differentiation. An interaction of PPARs during cardiovascular differentiation processes is proposed in this work.
Methods/Results:
The PPAR-gamma agonist ciglitazone (CGZ) inhibits cardiomyogenesis at all time points of differentiation (1然 to 50然), rosiglitazone (RGZ) (1然 to 20然) suppressed cardiomyogenesis at day 4+10, whereas GW9662 (antagonist of PPAR-gamma) stimulates cardiomyogenesis throughout differentiation. The beating frequency is increased following incubation with RGZ and GW9662, but reduced following incubation with CGZ.
RGZ and CGZ (1然, 10然) stimulated smooth muscle differentiation, and GW9662 (1然, 2然) inhibited smooth muscle differentiation.
RGZ and CGZ (10然) inhibited endothelial differentiation but CD31 is induced by GW9662 (1然, 2然).
It is known that agonists and antagonists of PPAR-gamma interact also with PPAR-alpha. We therefore studied PPAR-alpha expression following incubation with RGZ, CGZ and GW9662. RGZ and CGZ (both 10然) decreased PPAR-alpha expression, whereas GW9662 increased PPAR-alpha expression. This observation strengthens the publication of Sharifpanah et al., (2008) who described that treatment with PPARα agonists (WY14643, GW7647, and ciprofibrate) significantly increased cardiomyogenesis and expression of cardiac genes. In parallel endogenous ROS generation was increased following GW9662 treatment and RGZ induced a decrease of the ROS signal. CGZ treatment had no significant effect on ROS generation.
Conclusion:
RGZ and CGZ, known as PPAR-gamma agonists and GW9662, an antagonist of PPAR-gamma, control the activity of PPAR-gamma as well as the expression of PPAR-alpha. The subsequent changes in ROS level and differentiation of cardiomyocytes, endothelial cells and smooth muscle cells are a result of the cooperation of PPARs. Cardiomyocyte and endothel differentiation were cooperatively regulated whereas smooth muscle differentiation is inversely controlled.
To cite this abstract, please use the following information:
Acta Physiologica 2013; Volume 207, Supplement 694 :P029