Retinal pericytes control expression of nitric oxide synthase and endothelin-1 in microvascular endothelial cells

AR Martin, JR Bailie, T Robson, Stephanie McKeown, O Al-Assar, A McFarland, DG Hirst

    Research output: Contribution to journalArticle

    34 Citations (Scopus)

    Abstract

    Pericytes are known to communicate with endothelial cells by direct contact and by releasing cytokines such as TGF-beta. There is also strong evidence that pericytes act as regulators of endothelial cell proliferation and differentiation. We have investigated the effect of pericyte-conditioned medium (PCM) on proliferation of human microvascular endothelial cells in vitro, together with the expression of the vasoregulatory molecules, constitutive and inducible nitric oxide synthases (ecNOS and iNOS), and endothelin-1 (ET-1). Expression was measured at the mRNA level using semiquantitative RT-PCR for all three genes and at the protein level for ecNOS and iNOS using Western blotting. Growth curves for HMECs showed that PCM inhibits proliferation, eventually leading to cell death. Exposure to PCM repressed iNOS mRNA expression fivefold after 6 h. A similar, though delayed, reduction in protein levels was observed. ecNOS mRNA was slightly induced at 6 h, though there was no significant change in ecNOS protein. By contrast, ET-1 mRNA was induced 2.3-fold after 6 h exposure to PCM. We conclude that pericytes release a soluble factor or factors that are potent inhibitors of endothelial cell growth and promote vasoconstriction by up-regulating endothelin-1 and down-regulating iNOS. (C) 2000 Academic Press.
    LanguageEnglish
    Pages131-139
    JournalMicrovascular Research
    Volume59
    Issue number1
    Publication statusPublished - Jan 2000

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    Pericytes
    Endothelin-1
    Nitric Oxide Synthase
    Endothelial Cells
    Conditioned Culture Medium
    Messenger RNA
    Growth Inhibitors
    Proteins
    Nitric Oxide Synthase Type II
    Vasoconstriction
    Transforming Growth Factor beta
    Cell Differentiation
    Cell Death
    Western Blotting
    Cell Proliferation
    Cytokines
    Polymerase Chain Reaction
    Growth

    Cite this

    Martin, AR., Bailie, JR., Robson, T., McKeown, S., Al-Assar, O., McFarland, A., & Hirst, DG. (2000). Retinal pericytes control expression of nitric oxide synthase and endothelin-1 in microvascular endothelial cells. Microvascular Research, 59(1), 131-139.
    Martin, AR ; Bailie, JR ; Robson, T ; McKeown, Stephanie ; Al-Assar, O ; McFarland, A ; Hirst, DG. / Retinal pericytes control expression of nitric oxide synthase and endothelin-1 in microvascular endothelial cells. In: Microvascular Research. 2000 ; Vol. 59, No. 1. pp. 131-139.
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    abstract = "Pericytes are known to communicate with endothelial cells by direct contact and by releasing cytokines such as TGF-beta. There is also strong evidence that pericytes act as regulators of endothelial cell proliferation and differentiation. We have investigated the effect of pericyte-conditioned medium (PCM) on proliferation of human microvascular endothelial cells in vitro, together with the expression of the vasoregulatory molecules, constitutive and inducible nitric oxide synthases (ecNOS and iNOS), and endothelin-1 (ET-1). Expression was measured at the mRNA level using semiquantitative RT-PCR for all three genes and at the protein level for ecNOS and iNOS using Western blotting. Growth curves for HMECs showed that PCM inhibits proliferation, eventually leading to cell death. Exposure to PCM repressed iNOS mRNA expression fivefold after 6 h. A similar, though delayed, reduction in protein levels was observed. ecNOS mRNA was slightly induced at 6 h, though there was no significant change in ecNOS protein. By contrast, ET-1 mRNA was induced 2.3-fold after 6 h exposure to PCM. We conclude that pericytes release a soluble factor or factors that are potent inhibitors of endothelial cell growth and promote vasoconstriction by up-regulating endothelin-1 and down-regulating iNOS. (C) 2000 Academic Press.",
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    Martin, AR, Bailie, JR, Robson, T, McKeown, S, Al-Assar, O, McFarland, A & Hirst, DG 2000, 'Retinal pericytes control expression of nitric oxide synthase and endothelin-1 in microvascular endothelial cells', Microvascular Research, vol. 59, no. 1, pp. 131-139.

    Retinal pericytes control expression of nitric oxide synthase and endothelin-1 in microvascular endothelial cells. / Martin, AR; Bailie, JR; Robson, T; McKeown, Stephanie; Al-Assar, O; McFarland, A; Hirst, DG.

    In: Microvascular Research, Vol. 59, No. 1, 01.2000, p. 131-139.

    Research output: Contribution to journalArticle

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    T1 - Retinal pericytes control expression of nitric oxide synthase and endothelin-1 in microvascular endothelial cells

    AU - Martin, AR

    AU - Bailie, JR

    AU - Robson, T

    AU - McKeown, Stephanie

    AU - Al-Assar, O

    AU - McFarland, A

    AU - Hirst, DG

    PY - 2000/1

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    N2 - Pericytes are known to communicate with endothelial cells by direct contact and by releasing cytokines such as TGF-beta. There is also strong evidence that pericytes act as regulators of endothelial cell proliferation and differentiation. We have investigated the effect of pericyte-conditioned medium (PCM) on proliferation of human microvascular endothelial cells in vitro, together with the expression of the vasoregulatory molecules, constitutive and inducible nitric oxide synthases (ecNOS and iNOS), and endothelin-1 (ET-1). Expression was measured at the mRNA level using semiquantitative RT-PCR for all three genes and at the protein level for ecNOS and iNOS using Western blotting. Growth curves for HMECs showed that PCM inhibits proliferation, eventually leading to cell death. Exposure to PCM repressed iNOS mRNA expression fivefold after 6 h. A similar, though delayed, reduction in protein levels was observed. ecNOS mRNA was slightly induced at 6 h, though there was no significant change in ecNOS protein. By contrast, ET-1 mRNA was induced 2.3-fold after 6 h exposure to PCM. We conclude that pericytes release a soluble factor or factors that are potent inhibitors of endothelial cell growth and promote vasoconstriction by up-regulating endothelin-1 and down-regulating iNOS. (C) 2000 Academic Press.

    AB - Pericytes are known to communicate with endothelial cells by direct contact and by releasing cytokines such as TGF-beta. There is also strong evidence that pericytes act as regulators of endothelial cell proliferation and differentiation. We have investigated the effect of pericyte-conditioned medium (PCM) on proliferation of human microvascular endothelial cells in vitro, together with the expression of the vasoregulatory molecules, constitutive and inducible nitric oxide synthases (ecNOS and iNOS), and endothelin-1 (ET-1). Expression was measured at the mRNA level using semiquantitative RT-PCR for all three genes and at the protein level for ecNOS and iNOS using Western blotting. Growth curves for HMECs showed that PCM inhibits proliferation, eventually leading to cell death. Exposure to PCM repressed iNOS mRNA expression fivefold after 6 h. A similar, though delayed, reduction in protein levels was observed. ecNOS mRNA was slightly induced at 6 h, though there was no significant change in ecNOS protein. By contrast, ET-1 mRNA was induced 2.3-fold after 6 h exposure to PCM. We conclude that pericytes release a soluble factor or factors that are potent inhibitors of endothelial cell growth and promote vasoconstriction by up-regulating endothelin-1 and down-regulating iNOS. (C) 2000 Academic Press.

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    Martin AR, Bailie JR, Robson T, McKeown S, Al-Assar O, McFarland A et al. Retinal pericytes control expression of nitric oxide synthase and endothelin-1 in microvascular endothelial cells. Microvascular Research. 2000 Jan;59(1):131-139.