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

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

Research output: Contribution to journalArticle

39 Citations (Scopus)

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 increasedNOproduction. 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.

Original languageEnglish (US)
Pages (from-to)629-636
Number of pages8
JournalBlood
Volume119
Issue number2
DOIs
StatePublished - Jan 12 2012
Externally publishedYes

Fingerprint

Relaxin
Endothelial cells
Nitric Oxide
Bone
Endothelial Cells
Bone Marrow
Knockout Mice
Pregnancy
Cell Count
Endothelial Progenitor Cells
Gene Knockout Techniques
Peptide Receptors
Flow cytometry
Peptide Hormones
NG-Nitroarginine Methyl Ester
Vascular Endothelium
Phosphatidylinositol 3-Kinases
Vascular Diseases
Vasodilation
Cell Movement

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Segal, M. S., Sautina, L., Li, S., Diao, Y., Agoulnik, A. I., Kielczewski, J., ... Conrad, K. P. (2012). Relaxin increases human endothelial progenitor cell NO and migration and vasculogenesis in mice. Blood, 119(2), 629-636. https://doi.org/10.1182/blood-2011-04-346007

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.

In: Blood, Vol. 119, No. 2, 12.01.2012, p. 629-636.

Research output: Contribution to journalArticle

Segal, MS, Sautina, L, Li, S, Diao, Y, Agoulnik, AI, Kielczewski, J, McGuane, JT, Grant, MB & Conrad, KP 2012, 'Relaxin increases human endothelial progenitor cell NO and migration and vasculogenesis in mice', Blood, vol. 119, no. 2, pp. 629-636. https://doi.org/10.1182/blood-2011-04-346007
Segal MS, Sautina L, Li S, Diao Y, Agoulnik AI, Kielczewski J et al. Relaxin increases human endothelial progenitor cell NO and migration and vasculogenesis in mice. Blood. 2012 Jan 12;119(2):629-636. https://doi.org/10.1182/blood-2011-04-346007
Segal, Mark S. ; Sautina, Laura ; Li, Shiyu ; Diao, YanPeng ; Agoulnik, Alexander I. ; Kielczewski, Jennifer ; McGuane, Jonathan T. ; Grant, Maria B. ; Conrad, Kirk P. / Relaxin increases human endothelial progenitor cell NO and migration and vasculogenesis in mice. In: Blood. 2012 ; Vol. 119, No. 2. pp. 629-636.
@article{66a2b3610c54459d8b2cb5d2bce92f02,
title = "Relaxin increases human endothelial progenitor cell NO and migration and vasculogenesis in mice",
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 increasedNOproduction. 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.",
author = "Segal, {Mark S.} and Laura Sautina and Shiyu Li and YanPeng Diao and Agoulnik, {Alexander I.} and Jennifer Kielczewski and McGuane, {Jonathan T.} and Grant, {Maria B.} and Conrad, {Kirk P.}",
year = "2012",
month = "1",
day = "12",
doi = "10.1182/blood-2011-04-346007",
language = "English (US)",
volume = "119",
pages = "629--636",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "2",

}

TY - JOUR

T1 - Relaxin increases human endothelial progenitor cell NO and migration and vasculogenesis in mice

AU - Segal, Mark S.

AU - Sautina, Laura

AU - Li, Shiyu

AU - Diao, YanPeng

AU - Agoulnik, Alexander I.

AU - Kielczewski, Jennifer

AU - McGuane, Jonathan T.

AU - Grant, Maria B.

AU - Conrad, Kirk P.

PY - 2012/1/12

Y1 - 2012/1/12

N2 - 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 increasedNOproduction. 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.

AB - 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 increasedNOproduction. 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.

UR - http://www.scopus.com/inward/record.url?scp=84862907742&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862907742&partnerID=8YFLogxK

U2 - 10.1182/blood-2011-04-346007

DO - 10.1182/blood-2011-04-346007

M3 - Article

VL - 119

SP - 629

EP - 636

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -