Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/91823
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Relaxin increases human endothelial progenitor cell NO and migration and vasculogenesis in mice
Author: Segal, M.S.
Sautina, L.
Li, S.
Diao, Y.
Agoulnik, A.I.
Kielczewski, J.
McGuane, J.T.
Grant, M.B.
Conrad, K.P.
Citation: Blood, 2012; 119(2):629-636
Publisher: American Society of Hematology
Issue Date: 2012
ISSN: 0006-4971
1528-0020
Statement of
Responsibility: 
Mark S. Segal, Laura Sautina, Shiyu Li, YanPeng Diao, Alexander I. Agoulnik, Jennifer Kielczewski, Jonathan T. McGuane, Maria B. Grant, and Kirk P. Conrad
Abstract: The ovarian peptide hormone, relaxin, circulates during pregnancy, contributing to profound maternal vasodilation through endothelial and nitric oxide (NO)–dependent mechanisms. Circulating numbers of bone marrow–derived endothelial cells (BMDECs), which facilitate angiogenesis and contribute to repair of vascular endothelium, increase during pregnancy. Thus, we hypothesized that relaxin enhances BMDEC NO production, circulating numbers, and function. Recombinant human relaxin-2 (rhRLX) stimulated PI3K/Akt B-dependent NO production in human BMDECs within minutes, and activated BMDEC migration that was inhibited by L-NG-nitroarginine methyl ester. In BMDECs isolated from relaxin/insulin-like family peptide receptor 2 gene (Rxfp2) knockout and wild-type mice, but not Rxfp1 knockout mice, rhRLX rapidly increased NO production. Similarly, rhRLX increased circulating BMDEC number in Rxfp2 knockout and wild-type mice, but not Rxfp1 knockout mice as assessed by colony formation and flow cytometry. Taken together, these results indicate that relaxin effects BMDEC function through the RXFP1 receptor. Finally, both vascularization and incorporation of GFP-labeled BMDECs were stimulated in rhRLX-impregnated Matrigel pellets implanted in mice. To conclude, relaxin is a novel regulator of BMDECs number and function, which has implications for angiogenesis and vascular remodeling in pregnancy, as well as therapeutic potential in vascular disease.
Keywords: Endothelium, Vascular
Cells, Cultured
Stem Cells
Animals
Mice, Inbred C57BL
Mice, Knockout
Humans
Mice
Nitric Oxide
Relaxin
Receptors, G-Protein-Coupled
Flow Cytometry
Signal Transduction
Cell Differentiation
Cell Movement
Pregnancy
Vasodilation
Neovascularization, Physiologic
Female
Male
Proto-Oncogene Proteins c-akt
Phosphatidylinositol 3-Kinases
Rights: © 2012 by The American Society of Hematology
DOI: 10.1182/blood-2011-04-346007
Appears in Collections:Aurora harvest 2
Medicine publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.