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

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

Description

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)...[Show more]

dc.contributor.authorSegal, Mark S.
dc.contributor.authorSautina, Laura
dc.contributor.authorLi, Shiyu
dc.contributor.authorDiao, YanPeng
dc.contributor.authorAgoulnik, Alexander I.
dc.contributor.authorKielczewski, Jennifer
dc.contributor.authorMcGuane, Jonathan T.
dc.contributor.authorGrant, Maria B.
dc.contributor.authorConrad, Kirk P.
dc.date.accessioned2016-03-11T03:18:58Z
dc.date.available2016-03-11T03:18:58Z
dc.identifier.issn0006-4971
dc.identifier.urihttp://hdl.handle.net/1885/100222
dc.description.abstractThe 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.
dc.description.sponsorshipThis work was supported by Gatorade Research (M.S.S.), National Institutes of Health grants R01 HL067937 (K.P.C.), R01 HD037067 (A.I.A.), and R01 EY12601 and EY07739 (M.B.G.).
dc.publisherAmerican Society of Hematology
dc.rights© 2012 by The American Society of Hematology
dc.sourceBlood
dc.subjectanimals
dc.subjectcell differentiation
dc.subjectcells, cultured
dc.subjectendothelium, vascular
dc.subjectfemale
dc.subjectflow cytometry
dc.subjecthumans
dc.subjectmale
dc.subjectmice
dc.subjectmice, inbred c57bl
dc.subjectmice, knockout
dc.subjectnitric oxide
dc.subjectphosphatidylinositol 3-kinases
dc.subjectpregnancy
dc.subjectproto-oncogene proteins c-akt
dc.subjectreceptors, g-protein-coupled
dc.subjectrelaxin
dc.subjectsignal transduction
dc.subjectstem cells
dc.subjectvasodilation
dc.subjectcell movement
dc.subjectneovascularization, physiologic
dc.titleRelaxin increases human endothelial progenitor cell NO and migration and vasculogenesis in mice
dc.typeJournal article
local.description.notesAt the time of publication the author was affiliated with University of Florida.
local.identifier.citationvolume119
dc.date.issued2012-01-12
local.publisher.urlhttp://www.hematology.org/
local.type.statusPublished Version
local.contributor.affiliationMcGuane, J. T., The Australian National University
local.identifier.essn1528-0020
local.bibliographicCitation.issue2
local.bibliographicCitation.startpage629-36
local.bibliographicCitation.lastpage636
local.identifier.doi10.1182/blood-2011-04-346007
CollectionsANU Research Publications

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