**6. The vascular RAS and erythropoiesis**

RAS has been shown to result in progenitor cell senescence and suppression of differentiation and adherence in bone marrow-derived EPCs in Ang II infusion models. This inhibitory impact could be attenuated by the administration of AT1 receptor antagonists [31]. Previous reports have proved the crucial role of Ang II during erythropoiesis [33]. In studies using transgenic mice expressing human renin and angiotensinogen, a drastic rise in levels of erythropoietin was observed, which is a glycoprotein hormone that controls erythropoiesis. Genetic ablation of AT1 receptor from these mice reduced erythropoietin levels and restored haematocrit levels [34]. Also, ACE blockade has been concomitant with haematocrit decrease in vivo [35]. The idea of ACE and/or Ang II being contributed to erythropoiesis was further confirmed by a recent research in which ACE marked haematopoietic stem cells from human embryonic, fetal and adult haematopoietic tissues [36]. However, the mechanism of Ang II-associated regulation of erythropoiesis is mainly unclear. Most of these effects are observed during early phases of erythropoiesis [37]. As mentioned above, some researchers imply that Ang II acts indirectly via its effect on erythropoietin levels [38], whereas others do not agree with this link [39]. The other possible mechanism is proposed to be the involvement of JAK (Janus kinase)/STAT (signal transducer and activator of transcription) pathway. JAK/STAT pathway is known to be activated by Ang II [40].
