Aim: 

It is well established that peroxisome proliferator-activated receptor-g (PPAR-g) agonists improve insulin resistance and exert anti-inflammatory, anti-oxidative and anti-proliferate effects on vascular wall cells. The aim of this study was to assess the effect of PPAR-g agonists (rosiglitazone, ciglitazone) and antagonist (GW9662) on endothelial cell (EC), smooth muscle cell (SMC) and cardiac cell differentiation in ES-cell derived embryoid bodies (EBs).

Methodology: 

EBs (CGR8) were plated in Petri dishes on day 4 and incubated with different concentrations of rosiglitazone, ciglitazone and GW9662. The differentiation of ECs and SMCs was assessed on day 12, 14 and 16, by immunohistochemistry (a-smooth muscle actin and CD31) using confocal laser scanning microscopy and western blot technique for a-smooth muscle actin. For assessing cardiomyogenesis the beating frequency and the number of beating areas of EBs were determined.

Results: 

Rosiglitazone stimulated SMC and cardiomyocyte differentiation, whereas ciglitazone suppressed SMC and cardiomyocyte differentiation. In contrast rosiglitazon inhibited endothelial differentiation, whereas ciglitazone stimulated endothelial differentiation. GW9662 suppressed SMC differentiation and stimulated endothelial differentiation as well as cardiomyocyte differentiation.

Conclusion: 

The effects of rosiglitazone and ciglitazone on EC, SMC and cardiomyocyte differentiation are different, despite of the fact that both agents are well described PPAR-g agonists.