**3. The RAS and ESCs**

ESCs are pluripotent cells capable of differentiation into different cells such as cardiomyocytes, and endothelial cells have been considered as a source of regenerative medicine [1]. For instance, ESC-derived endothelial cells have therapeutic effects via the increment of angiogenesis and heart functionality [2]. PI3/Akt-signalling pathway has been shown to be linked with human ESC-derived cardiomyocyte proliferation in vitro [3]. RAS stimulation activates PI3/AKT pathway, while the inhibition of RAS increases Akt phosphorylation [4], which might influence the proliferation of ESCs. High survival rate after transplantation is another main, noteworthy issue about ESCs [5].

RAS is a novel regulatory candidate, which controls the development of ESCs into different cell types. It has been reported that the expression AT1 receptors were detected in an early stage of human ESCs differentiation. Since the addition of Ang II results in the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and Jun N-terminal (JNK) 1/2, this peptide is capable of acting as signalling molecules and thus it could regulate differentiation [6]. Moreover, Ang II has been shown to increase glucose uptake in ESCs [7] and induce mitogenic effect, possibly through protein kinase C and mitogen-activated protein kinase (MAPK)-signalling pathways. Interestingly, exposure to a high glucose niche in the presence of Ang II has been shown to produce a synergistic impact on ESC proliferation [8].
