Angiotensin II promotes cardiac differentiation of embryonic stem cells via angiotensin type 1 receptor

• ESCs differentiated into cardiomyocytes after induction with vitamine C.
• AT1R was expressed in ESC-CMs.
• Ang II promoted cardiac differentiation of ESCs.
• Losartan alone without exogenous Ang II had no effect on cardiac differentiation.
• Ang II stimulated the cardiac differentiation via ERK, p38 and JNK activation.

As embryonic stem cells (ESCs) represent an attractive candidate cell source for obtaining cardiomyocytes to be used in cell replacement therapy, it is thus of considerable importance to understand the mechanism by which cardiac differentiation is regulated. In previous studies, we have shown that angiotensin type 1 receptor (AT1R) expressed in cardiomyocytes derived from mouse embryonic stem cells. However, little is known about the role of AT1R in cardiac differentiation, which plays a key role in cardiac physiology and pharmacology. In the present study, we demonstrated that AT1R agonist significantly enhanced cardiac differentiation as determined by increased percentage of beating embryoid bodies and a higher expression level of cardiac markers. On the contrary, AT1R agonist stimulated differentiation was reversed in the presence of AT1R antagonist. In addition, by administering selective inhibitors we found that the effect of AT1R was driven via extracellular-signal regulated kinase, c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase pathways. These findings suggest that AT1R signaling plays a key role in cardiac differentiation of ESCs.