Relaxin increases human endothelial progenitor cell NO and migration and vasculogenesis in mice

Date

2012-01-12

Authors

Segal, Mark S.
Sautina, Laura
Li, Shiyu
Diao, YanPeng
Agoulnik, Alexander I.
Kielczewski, Jennifer
McGuane, Jonathan T.
Grant, Maria B.
Conrad, Kirk P.

Journal Title

Journal ISSN

Volume Title

Publisher

American Society of Hematology

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-N(G)-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.

Description

Keywords

animals, cell differentiation, cells, cultured, endothelium, vascular, female, flow cytometry, humans, male, mice, mice, inbred c57bl, mice, knockout, nitric oxide, phosphatidylinositol 3-kinases, pregnancy, proto-oncogene proteins c-akt, receptors, g-protein-coupled, relaxin, signal transduction, stem cells, vasodilation, cell movement, neovascularization, physiologic

Citation

Source

Blood

Type

Journal article

Book Title

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