The peptide network regulated by angiotensin converting enzyme (ACE) in hematopoiesis

Abstract

The concept of a local bone marrow renin-angiotensin system (RAS) has been introduced and accumulating evidence suggests that the local RAS is actively involved in hematopoiesis. Angiotensin converting enzyme (ACE) is a key player in the RAS and makes the final effector angiotensin II. Besides angiotensin II, ACE also regulates a panel of bioactive peptides, such as substance P, Ac-SDKP and angiotensin 1-7. These peptides have also been individually reported in the regulation of pathways of hematopoiesis. In this setting, an ACE-regulated peptide network orchestrating hematopoiesis has emerged. Here, we focus on this peptide network and discuss the roles of ACE and its peptides in aspects of hematopoiesis. Special attention is given to the recent revelation that ACE is a bona fide marker of hematopoietic stem cells.

Figure 1

BM local ACE regulates peptides for hematopoiesis. Systemically, Ang I, Ang II, Ac-SDKP and Ang 1–7 are produced in other tissues and shipped to the BM through circulation, and SP is released from the nerve ending projecting to the BM (in the vicinity of stroma). These peptides are also produced from BM tissue by the contribution of both stromal cells and hematopoietic cells. ACE releases Ang II from Ang I and degrades the bioactive SP, Ac-SDKP and Ang 1–7. Both stromal cells and hematopoietic cells are equipped with AT1 receptor and NK1 receptor and mediate the action of Ang II and SP, respectively. Ac-SDKP is known to act on hematopoietic cells but its receptor has not been identified. Mas, the receptor for Ang 1–7, can been detected in BM. These peptides thus can either directly stimulate hematopoietic cells or perform their actions through stromal cells.