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Basic Res Cardiol. 2018 Mar 17;113(3):18. doi: 10.1007/s00395-018-0677-y.

Role of the angiotensin-converting enzyme in the G-CSF-induced mobilization of progenitor cells.

Author information

1
Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
2
German Centre for Cardiovascular Research (DZHK), Partner Site Rhein-Main, Frankfurt am Main, Germany.
3
Blood Donor Services Zürich and Chur, Swiss Red Cross, Zurich, Switzerland.
4
Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany. fleming@em.uni-frankfurt.de.
5
German Centre for Cardiovascular Research (DZHK), Partner Site Rhein-Main, Frankfurt am Main, Germany. fleming@em.uni-frankfurt.de.

Abstract

In addition to being a peptidase, the angiotensin-converting enzyme (ACE) can be phosphorylated and involved in signal transduction. We evaluated the role of ACE in granulocyte-colony-stimulating factor (G-CSF)-induced hematopoietic progenitor cell (HPC) mobilization and detected a significant increase in mice-lacking ACE. Transplantation experiments revealed that the loss of ACE in the HPC microenvironment rather than in the HPCs increased mobilization. Indeed, although ACE was expressed by a small population of bone-marrow cells, it was more strongly expressed by endosteal bone. Interestingly, there was a physical association of ACE with the G-CSF receptor (CD114), and G-CSF elicited ACE phosphorylation on Ser1270 in vivo and in vitro. A transgenic mouse expressing a non-phosphorylatable ACE (ACES/A) mutant demonstrated increased G-CSF-induced HPC mobilization and decreased G-CSF-induced phosphorylation of STAT3 and STAT5. These results indicate that ACE expression/phosphorylation in the bone-marrow niche interface negatively regulates G-CSF-induced signaling and HPC mobilization.

KEYWORDS:

ACE inhibitor; ACE phosphorylation; Angiotensin-converting enzyme; Progenitor cell mobilization

PMID:
29549541
DOI:
10.1007/s00395-018-0677-y
[Indexed for MEDLINE]

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