The hematopoietic system: a new niche for the renin-angiotensin system
P Corvol, C Hubert, K Savary & J Gasc
The renin angiotensin system (RAS) is well known for its role in the regulation of blood pressure and fluid homeostasis. Blockers of the RAS are widely used for the treatment of hypertension, cardiac failure and chronic renal insufficiency. Angiotensin I converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are usually quite well tolerated. In addition to the systemic effect of the RAS, evidence for an autocrine/paracrine role of this system has been well documented. The angiotensin peptides may act locally as growth factors or inhibitors and exert effects in cardiac, vascular, renal and in other various tissues, similarly to cytokines. Recent data show that the renin system may also control hematopoiesis at its different stages. This unsuspected finding comes from early observations made in patients treated by ACE inhibitors or ARBs. We will see how different experimental models of genetically-engineered mice and the study of hematopoiesis in chick embryo allow to decipher the mechanism of action of the renin system in hematopoiesis. The renin system, and particularly angiotensin II, plays a role at the different steps of hematopoiesis, notably during the first wave of hematopoiesis in the chick embryo (primitive hematopoiesis): all the components of the renin system are expressed in close proximity to the blood islands in the yolk sac before the circulations starts, and this primitive hematopoiesis is dependent of the integrity of the RAS. The RAS is also involved during the adult phase of hematopoiesis in the fetus (definitive hematopoiesis). In addition, the renin system is implicated in the reconstitutive hematopoiesis following experimental irradiation in mice as inhibitors of this system improve the hematopoietic recovery in this situation. The clinical relevance and therapeutic applications of these findings offer a new area of research.