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

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

Research output: Contribution to journalArticle

40 Scopus citations

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

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Segal, M. S., Sautina, L., Li, S., Diao, Y. P., Agoulnik, A. I., Kielczewski, J., McGuane, J. T., Grant, M. B., & 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